A Potential Oligogenic Etiology of Hypertrophic Cardiomyopathy, A Classic Single Gene Disorder
PMID:28223422
Gene:MYL2
HGNC ID:7583
2,078 Matching Annotations
- Last 7 days
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Family M1
Case1: A 68-year-old female
DiseaseAssertion: dilated cardiomyopathy (DCM), with the MYH7 p.Lys637Glu (K637E) variant identified in the affected patient. The study investigated sarcomeric gene variants associated with DCM
FamilyInfo: The proband's father (M1, II:3) died suddenly at 36 years of age, 2 years after being diagnosed with DCM.
ParentalTesting: Yes from father
CasePresentingHPOs: HP:0011664, HP:0011713, HP:0003677, HP:0001635,
CaseHPOFreeText: was diagnosed as having left ventricular non-compaction (LVNC) based on echocardiography. A left bundle branch block on her ECG. Echocardiography revealed LVNC and she has had a slow progression towards heart failure and an increasing dilatation of her left ventricle. Age 48 at onset, left ventricular end diastolic diameter 59 mm, left ventricular ejection fraction 25%, ventricular extrasystoles for arrhythmia.
CaseNotHPOs:NR
CaseNotHPOFreeText:NR
CasePreviousTesting:NR
Genotyping Method: genetically screened, also using GenBank with PCR by amplifying the coding region
FunctionalAnalysis:NR
Variant: NM_000257.4:c.1909A>G
ClinVar: 1329402
CAID:CA389049558
gnomAD: NR
AdditionalInfo: NR
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The role of sarcomere gene mutations in patients with idiopathic dilated cardiomyopathy
PMID: 19293840
Gene: MYH7
HGNC ID: 7577
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Cardiac troponin T mutation in familial cardiomyopathy with variable remodeling and restrictive physiology
PMID: 18651846
Gene: TNNT2
HGNC ID: 11949
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ashpublications.org ashpublications.org
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A potential role for α-actinin in inside-out αIIbβ3 signaling
PMID: 20940419
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: No proband or variant information; however, there is potential experimental assay information
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www.sciencedirect.com www.sciencedirect.com
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Inherited traits affecting platelet function
PMID: 18180086
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article gives background information on GT; there is no mention of GT probands with variants in ITGA2B and/or ITGB3
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link.springer.com link.springer.com
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Successful management of perioperative hemostasis in a patient with Glanzmann thrombasthenia who underwent a right total mastectomy
PMID: 27696190
Gene: ITGA2B
HGNC: 6138
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reader.elsevier.com reader.elsevier.com
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Inhibition of Platelet Aggregation byAbciximab but Not by Aspirin Can BeDetected by a New Point-of-Care Test, the Hemostatus
PMID: 10418797
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient; however, there is no mention of variants in ITGA2B and/or ITGB3; therefore, there is insufficient evidence
PreviouslyPublished: The GT patient in this article has been previously published in this PMID: 2180491
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ashpublications.org ashpublications.org
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Recombinant factor VIIa enhances deposition of platelets with congenital or acquired αIIbβ3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor–independent thrombin generation
PMID: 12411291
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT probands with variants in ITGA2B and/or ITGB3 therefore there is no evdience; however, there may be potenetial experimental assay information
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Interactionofhumanplateletswithlamininandidentificationofthe67kDalamininreceptoronplatelets
PMID: 1826081
Gene: ITGA2B and ITGB3 (we are noting these gene names even though there is no evidence for GT in this article, because we are curating for these genes-- CThaxton advised it would be a good idea to always note down Genes and HGNC)
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report. The studies performed in this article were undertaken to characterize the interaction of platelets with laminin.
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Local file Local file
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Are bone defects in rare patients with Glanzmann’s thrombastheniaassociated withITGB3orITGA2Bmutations?
PMID: 21557682
Gene: ITGA2B
HGNC: 6138
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Successful Management of Acute Catastrophic Juvenile Vaginal Bleeding in Glanzmann's Thromboasthenia by Uterine Tamponade: A Case Report and Review of The Literature
PMID: 22928124
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article reports a case of acute catastrophic vaginal bleeding in a girl, who was diagnosed with GT and responded to uterine tamponade for acute control of vaginal bleeding; however, no variants in ITGA2B and/or ITGB3 are mentioned in this article therefore we have insufficient evidence
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www.tandfonline.com www.tandfonline.com
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FLOW CYTOMETRIC ANALYSIS OF PLATELET SURFACE GLYCOPROTEINS IN THE DIAGNOSIS OF BERNARD-SOULIER SYNDROME
PMID: 9021812
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report
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reader.elsevier.com reader.elsevier.com
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VISUALIZATION OF PLATELET GLYCOPROTEINS Ib AND IIIa BY IMMUNOENZYMATIC STAIN USING AVIDIN-BIOTIN PEROXIDASE COMPLE
PMID: 1788826
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence
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watermark.silverchair.com watermark.silverchair.com4712.pdf1
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Truncation of Glycoprotein (GP) IIIa (D616-762) Prevents ComplexFormation With GPIIb: Novel Mutation in Exon 11 of GPIIIaAssociated With Thrombasthenia
PMID: 9845537
Gene: ITGB3
HGNC: 6156
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www.ahajournals.org www.ahajournals.org
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Platelet Glycoprotein IIb/IIIa Receptors and Glanzmann’s Thrombasthenia Deborah L. French and Uri SeligsohnFrom the Mount Sinai School of Medicine (D.L.F.), New York, NY, and The Chaim Sheba Medical Center (U.S.), Tel-Hashomer, Israel.
PMID: 10712380
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This review mentions many variants in ITGA2B and ITGB3; however, there are no probands to tie these variants to therefore there is insufficient evidence
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Double heterozygosity of the GPIIb gene in a Swiss patient with Glanzmann's thrombasthenia
PMID: 9734640
Gene: ITGA2B
HGNC: 6138
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend
PMID: 18840725
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article is a review discussing the integrin αIIbβ3, there is no mention of probands with variants in ITGA2B and/or ITGB3
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reader.elsevier.com reader.elsevier.com
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Inherited bleeding disorders: disorders of plateletadhesion and aggregation
PMID: 9351872
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article is a review on GT
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www.haematologica.org www.haematologica.org
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A simple, novel and robust test to diagnose type I Glanzmann thrombasthenia
PMID: 18450741
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InusufficientEvidence: This article used a bifunctional bioengineered disintegrin/alkaline phosphatase hybrid protein ErAPv to evaluate 14 consecutive cases of Glanzmann thrombasthenia and 20 normal healthy controls. Thererefore, GT probands are mentioned; however, no specific variants in ITGA2B and/or ITBG3 have been mentioned in these patients
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A Rare Case of Bleeding Disorder: Glanzmann's Thrombasthenia
PMID: 29063905
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case of an individual with Glanzmann thrombasthenia; however, no specific variants mentioned in proband.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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High-level transgene expression in induced pluripotent stem cell–derived megakaryocytes: correction of Glanzmann thrombasthenia
PMID: 24335497
Gene: ITGA2B
HGNC: 6138
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www.jimmunol.org www.jimmunol.org
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Human IgG Monoclonal Anti-αIIbβ3-Binding Fragments Derived from Immunized Donors Using Phage Display
PMID: 11823541
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions 1 GT proband; however, variants in ITGA2B and/or ITGB3 are not mentioned.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Iraqi-JewishandArabpopulationsinIsrael
PMID: 2014236
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article does not mention specific case reports- rather, this article mentions two different populations harboring variants. I have annotated the 2 variants each cohort harbors
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www.sciencedirect.com www.sciencedirect.com
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Should studies on Glanzmann thrombasthenia not be telling us more about cardiovascular disease and other major illnesses?
PMID: 28395882
Gene: ITGA2B and ITGB3
HGNC: 6139 and 6156
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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From thrombasthenia to next generation thrombocytopenia: Neonatal alloimmune thrombocytopenia induced by maternal Glanzmann thrombasthenia
PMID: 30216638
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions mothers with GT and their newborns. Table 1 shows very general/vague genetic data for the mothers, it is not easy to determine what the actual genetic defects are from Table 1; therefore, there is insufficient evidence
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stke.sciencemag.org stke.sciencemag.org
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Platelets contribute to amyloid-β aggregation in cerebral vessels through integrin αIIbβ3–induced outside-in signaling and clusterin release
PMID: 27221710
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT probands with variants in ITGA2B or ITGB3
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Local file Local fileuntitled1
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Allogeneic Hematopoietic Stem Cell Transplantation in Glanzmann Thrombasthenia Complicated by Platelet Alloimmunization
PMID: 21567370
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with GT; however, no mention of the proband with variants in ITGA2B and ITGB3
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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HomologousRecombinationamongThreeIntrageneAluSequencesCausesanInversion-DeletionResultingintheHereditaryBleedingDisorderGlanzmannThrombasthenia
PMID: 8317479
Gene: ITGB3
HGNC: 6156
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A Two–Amino Acid Insertion in the Cys146–Cys167 Loop of the aIIb Subunit Is Associated with a Variant of Glanzmann Thrombasthenia
PMID: 9739052
Gene: ITGA2B
HGNC: 6138
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Arthropathy-like findings and a carpal tunnel syndrome as the presenting features of Scheie syndrome: Three cases from the same family
Article not publicly available through PubMed.
PMID: 30511553
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Treatment of latent tuberculosis in a child with mucopolysaccharidosis type I receiving enzyme replacement therapy: A case report
PMID: 36052356
Gene: IDUA
Disease: MPS1
Inheritance: Autosomal recessive
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www.tandfonline.com www.tandfonline.com
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A novel 196 Leu to Pro substitution in the β3subunit of the αIIbβ3 integrin in a patient with avariant form of Glanzmann thrombasthenia
PMID: 11897046
Gene: ITGB3
HGNC: 6156
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www.jbc.org www.jbc.org
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The Role of Conserved Amino Acid Motifs within theIntegrinb3Cytoplasmic Domain in Triggering FocalAdhesion Kinase Phosphorylation*
PMID: 9065456
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B and/or ITGB3; however, no specific GT probands are mentioned harboring these variants mentioned therefore there is insufficient evidence
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Qualitative disorders of platelets and megakaryocytes
PMID: 16102044
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article mentions variants in ITGA2B; however, the variants are not linked to individuals bearing them therefore we have insufficient evidence
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients
PMID: 16104882
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: The purpose of our study was to determine the frequency of alloimmunisation against platelets and leukocytes in multiply transfused Tunisian patients; there are 3 GT probands in this article; however, no mention of variants in ITGA2B and/or ITBG3; therefore, we have insufficient evidence
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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A naturally occurring mutation near the C terminus of the β‐propeller of αIIb impair the transport of αIIbβ3 complexes from the endoplasmic reticulum to the Golgi apparatus
PMID: 15946231
Gene: ITGA2B
HGNC: 6138
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Platelet collagen receptor Glycoprotein VI-dimer recognizesfibrinogen and fibrin through their D-domains, contributing toplatelet adhesion and activation during thrombus formation
PMID: 29210180
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: Article does not mention GT probands with specific variants in ITGA2B and/or ITGB3
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Novel mutations in Thai patients with glanzmann thrombasthenia
PMID: 28888044
Gene: ITGA2B
HGNC: 6138
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Local file Local file
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A 10-Base-Pair Deletion in the Gene Encoding Platelet GlycoproteinIIb Associated with Glanzmann Thrombasthenia in a Horse
PMID: 17338169
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article discusses a 10 base pair deletion in GT; however, in a horse, not human therefore there is insufficient evidence
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watermark.silverchair.com watermark.silverchair.com3212.pdf1
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Molecular Basis for Glanzmann’s Thrombasthenia (GT) in a Compound Heterozygote With Glycoprotein IIb Gene: A Proposal for the Classification of GT Based on the Biosynthetic Pathway of Glycoprotein IIb-IIIa Complex
PMID: 1317725
Gene: ITGA2B
HGNC: 6138
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journals.lww.com journals.lww.com
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Glanzmann thrombasthenia detected because of knee hemarthrosis: a case report
PMID: 20736850
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with GT; however, no variants in ITGA2B or ITGB3 are mentioned
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watermark.silverchair.com watermark.silverchair.com1857.pdf1
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A Point Mutation in the Integrin p3 Cytoplasmic Domain (S752 + P) Impairs Bidirectional Signaling Through aIIbP3 (Platelet Glycoprotein IIb-IIIa)
PMID: 8080992
Gene: ITGB3
HGNC: 6138
InsufficentEvidence: This article mentions a variant in ITGB3; however, the article does not mention a GT case report with the variant in detail, rather this paper cites another paper of a proband harboring the variant of interest
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Double heterozygosity for a novel missense mutation of Ile304 to Asn in addition to the missense mutation His280 to Pro in the integrin β3 gene as a cause of the absence of platelet αIIbβ3 in Glanzmann's thrombasthenia
PMID: 15634267
Gene: ITGB3
HGNC: 6156
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journals.sagepub.com journals.sagepub.com
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Glanzmann'sThrombastheniaProposedOptimalManagementDuringSurgeryandDelivery
PMID: 12812388
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a 34 year old proband with GT; however, there is no mention of variants in ITGA2B and/or ITGB3 in the proband that is mentioned
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Three novel β-propeller mutations causing Glanzmann thrombasthenia result in production of normally stable pro-αIIb, but variably impaired progression of pro-αIIbβ3 from endoplasmic reticulum to Golgi
PMID: 16359515
Gene: ITGA2B
HGNC: 6138
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search.proquest.com search.proquest.com
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Successful surgery using recombinant factor VIIa for recurrent, idiopathic nonulcer duodenal bleeding in a patient with Glanzmann's thrombasthenia
PMID: 12353868
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Spontaneous hemarthrosis in combined Glanzmann thrombasthenia and type 2N von Willebrand disease.
PMID: 24418945
Gene: ITGA2B
HGNC: 6138
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watermark.silverchair.com watermark.silverchair.com
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A second case of variant of Glanzmann'sthrombasthenia due to substitution ofplatelet GPIIIa (integrin (33) Arg214 by Tr
PMID: 7509233
Gene: ITGB3
HGNC: 6156
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www.tandfonline.com www.tandfonline.com
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Glanzmann's thrombasthenia in North Indians: Sub classification and carrier detection by flow cytometry
PMID: 19172516
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions individuals with GT; however, there are no variants in ITGA2B and/or ITGB3 mentioned here
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ashpublications.org ashpublications.org
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A Leu262Pro mutation in the integrin β3 subunit results in an αIIb-β3 complex that binds fibrin but not fibrinogen
PMID: 10891446
Gene: ITGB3
HGNC: 6156
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onlinelibrary.wiley.com onlinelibrary.wiley.com
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Insertion of a C in the exon 28 of integrin αIIb gene leading to a frameshift mutation is responsible for Glanzmann thrombasthenia in a Japanese case
PMID: 15748238
Gene: ITGA2B
HGNC: 6138
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www.fertstert.org www.fertstert.org
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Endometriosis in two sisters with Glanzmann's thrombasthenia
PMID: 19647234
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions two individuals with GT; however, there is no mention of variants in ITGA2B and/or ITGB3
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watermark.silverchair.com watermark.silverchair.com369.pdf1
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Platelet Glycoprotein IIb-III, (ffIIbp3 Integrin) Confers Fibrinogen- and Ac tiva tion-Dependen t Aggregation on Heterologous Cells
PMID: 2070074
Gene: N/A
HGNC: N/A
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence
Note: Although there is no evidence regarding GT probands and variants-- there is some experimental assay evidence, where methods for the experiment may be useful
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Glanzmann's thrombasthenia and pregnancy: report of a case and literature review
PMID: 22384307
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with GT however there are no variants in ITGA2B or ITGB3 mentioned
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Local file Local file
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Inherited platelet disorders
PMID: 22726100
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This review mentions variants in ITGA2B and ITGB3; however, variants are not tied to specific probands therefore there is insufficient evidence
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Local file Local file
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Inherited platelet disorders and oral health
PMID: 22583386
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention probands or variants with GT however this has a general summary of Glanzmann thrombasthenia
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pdfs.semanticscholar.org pdfs.semanticscholar.org
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Anovel Ser123Pro substitution in the MIDAS domainof integrin 3 associated with variant
PMID: 15590407
Gene: ITGB3
HGNC: 6156
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pdf.sciencedirectassets.com pdf.sciencedirectassets.com
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Glanzmann thrombasthenia: An update
PMID: 19854165
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article describes many variants in ITGA2B and ITGB3 however no probands to tie variants to therefore insufficient evidence
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www.jisppd.com www.jisppd.com
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Hematological and surgical management in Glanzmann's thrombasthenia: A case report
PMID: 24739923
Gene: ITGA2B and/or ITGB3 (These genes may be involved since this patient has GT)
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with Glanzmann thrombasthenia; however, there are no ITGA2B or ITGB3 variants in this proband
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files.libcom.org files.libcom.org
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Norethisterone therapy for bleeding due to gastrointestinaltelangiectases in Glanzmann’s thrombasthenia
PMID: 9504647
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
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pdfs.semanticscholar.org pdfs.semanticscholar.org45-1.pmd1
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Pyelolithotomy in a patient with Glanzmann thrombasthenia andantiglycoprotein IIb/IIIa antibodies: the shortest possibleduration of treatment with recombinant activated factor VII andplatelet transfusions
PMID: 12718376
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: Thus article mentions a Glanzmann thrombasthenia proband; however, no variants in ITGA2B and/or ITGB3 were reported in this patient
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onlinelibrary-wiley-com.libproxy.lib.unc.edu onlinelibrary-wiley-com.libproxy.lib.unc.edu
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Role of RFLP using TspRI for carrier detection in Glanzmann’s thrombasthenia: a report on two families M. KANNAN Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author B. K. YADAV Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author F. AHMAD Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author R. SAXENA Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author
PMID: 19170775
Gene: ITGA2B
HGNC: 6138
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Local file Local file
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DDAVP-induced enhancement of platelet retention: Its dependence on platelet-von Willebrand Factor and the platelet receptor GP IIb/IIIa
PMID: 1499698
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient (29 years old); however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence. The aim of the present study was to investigate the mechanism by which DDAVP induces increased platelet adhesiveness, as measured in a platelet retention test.
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watermark.silverchair.com watermark.silverchair.com75.pdf1
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Plat el et Vitro nec t in Receptor Exp res s ion Differentiates Iraqi - Jewi s h From Arab Patients With Glanzmann Thrombasthenia in Israel
PMID: 1949709
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article examined platelets of the Iraqi-Jewish and Arab Glanzmann thrombasthenia population; however, no specific proband information or variants in ITGA2B and/or ITGB3 were mentioned. This could be classified as "NoEvidence"; however, due to the fact the article mentioned two specific populations, I have noted it under "InsufficientEvidence"
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Deep Vein Thrombosis, Raynaud's Phenomenon, and Prinzmetal Angina in a Patient with Glanzmann Thrombasthenia
PMID: 23346430
Gene: ITGA2B
HGNC: 6138
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Local file Local file
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Presentation and Pattern of Symptoms in 382 PatientsWith Glanzmann Thrombasthenia in Iran
PMID: 15389911
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article looks at the presentation and pattern of symptoms in 382 patients with GT. There are no variants associated with probands in ITGA2B and/or ITBG3
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Use of rFVIIa in 4 children with Glanzmann thrombasthenia.
PMID: 17023825
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions individuals with GT; however, there is no mention of these individuals bearing variants in ITGA2B and/or ITBG3
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www.jstage.jst.go.jp www.jstage.jst.go.jpen1
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Acute Epidural Hematoma in a PatientWith Glanzmann's Thrombasthenia—Case Report—
PMID: 21030808
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a 7 year old girl with GT; however, there are no variants in ITGA2B or ITGB3 mentioned in this article
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Founder effect and estimation of the age of the French Gypsy mutation associated with Glanzmann thrombasthenia in Manouche families
PMID: 21487445
Gene: ITGA2B
HGNC: 6138
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-
Local file Local file
-
Acquired thrombasthenia due to GPIIbIIIaplatelet autoantibodies in a 4-yr-old child
PMID: 15748238
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions proband with acquired thrombasthenia; however, there is no mention of variants in ITGA2B and/or ITGB3
-
-
Local file Local file
-
PeriodontalManagementofGlanzmann'sThrombasthenia:Reportof3Cases
PMID: 8866321
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions 3 Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in these individuals; therefore, we have insufficient evidence
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
A Glanzmann’s mutation in β3 integrin specifically impairs osteoclast function
PMID: 11342577
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B/ITGB3; however, there is no mention of individual(s) with GT therefore we have insufficient evidence
-
-
reader.elsevier.com reader.elsevier.com
-
Hematologically Important Mutations: Glanzmann Thrombasthenia
PMID: 9215749
Gene: ITGA2B and ITGB3
HGNC: 6138 abd 6156
-
-
Local file Local fileuntitled1
-
aIIbb3 Integrin: New Allelic Variants in GlanzmannThrombasthenia, Effects onITGA2BandITGB3mRNASplicing, Expression, and Structure–Function
PMID: 20020534
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Characterization of the cDNA and genomic DNA sequence encoding for the platelet integrin alpha IIB and beta III in a horse with Glanzmann thrombasthenia
PMID: 22210999
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article mentions a variant in ITGA2B; however, it is examined in a horse not human
-
-
europepmc.org europepmc.org
-
Novel Mutations in the GPIIb and GPIIIa Genes in Glanzmann Thrombasthenia
PMID: 21113249
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
-
-
link.springer.com link.springer.com
-
Molecular analysis of a patient with type I Glanzmannthrombasthenia and clinical impact of the presenceof anti-aIIbb3 alloantibodies
PMID: 21136216
Gene: ITGB3
HGNC: 6138
-
-
Local file Local file
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The Level of Laboratory Testing Requiredfor Diagnosis or Exclusion of a PlateletFunction Disorder Using Platelet Aggregationand Secretion Assays
PMID: 19408197
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article provides background information on Glanzmann thrombasthenia; however, does not mention probands or variants in ITGA2B and ITGB3
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Thrombin generation assays: accruing clinical relevance.
PMID: 15257016
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT patients with variants in ITGA2B and/or ITGB3; however, this may be useful for experimental assay purposes
-
-
Local file Local file
-
DentalConsiderationsforaGlanzmann'sThrombastheniaPatient:CaseReport
PMID: 8724714
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
-
-
pdfs.semanticscholar.org pdfs.semanticscholar.org
-
Platelet Fibrinogen and Vitronectin in Glanzmann Thrombasthenia: Evidence Consistent With Specific Roles for Glycoprotein IIb/IIIa and a,P3 Integrins in Platelet Protein Trafficking
PMID: 1726706
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report
-
-
-
A Ser752fiPro substitution in the cytoplasmic domain ofb3in a Glanzmann thrombasthenia variant fails to preventinteractions between theaIIbb3 integrin and the plateletgranule pool of fibrinogen
PMID: 12199799
Gene: ITGB3
HGNC: 6156
-
-
www.tandfonline.com www.tandfonline.com
-
ITGA2B and ITGB3 gene mutations associated withGlanzmann thrombasthenia
PMID: 29125375
Gene: ITGA2B and ITBG3
HGNC: 6138 and 6156
NoEvidence This article gives a general overview of Glanzmann thrombasthenia, it does not discuss a proband or variants within probands.
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Congenital disorders associated with platelet dysfunctions.
PMID: 18278172
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions Glanzamnnt thrombasthenia variants; however, these variants are not tied to individual probands
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Hematuria: An uncommon presentation of Glanzmann's thrombasthenia—Lessons learnt
PMID: 20535297
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case study of a 55 year old male with GT; however, no variants in ITGA2B/ITGB3 are presented here
-
-
www.jbc.org.libproxy.lib.unc.edu www.jbc.org.libproxy.lib.unc.edu
-
Platelet-derived Microparticle Formation Involves Glycoprotein IIb-IIIa
PMID: 8325838
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and ITGB3
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients
PMID: 30792900
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156 respectively as shown above
-
-
Local file Local file
-
First description of an IgM monoclonal antibody causingaIIbb3integrin activation and acquired Glanzmannthrombasthenia associated with macrothrombocytopenia
PMID: 30868743
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156, respectively as shown above
InsufficientEvidence: Article discusses case report; however, no variants were reported in either ITGA2B or ITGB3 among sequencing analysis for proband.
-
-
watermark.silverchair.com watermark.silverchair.com977.pdf1
-
The Molecular Genetic Basis of Glanzmann’s Thrombasthenia in a Gypsy Population in France: Identification of a New Mutation on the &IIb Gene
PMID: 7620188
Gene: ITGA2B
HGNC: 6138
Note: Article mentions, under materials and methods, that the group being studied are two different families (I and II) belonging to the French gypsy community; however, in the results section the article focuses on patient V.17 from Family 1- therefore patient V.17 is annotated as the proband in this article
-
-
www.sciencedirect.com www.sciencedirect.com
-
A novel approach using ancillary tests to guide treatment of Glanzmann thrombasthenia patients undergoing surgical procedures
PMID: 30078718
Gene: ITGB3
HGNC: 6156
-
-
www-thieme-connect-com.libproxy.lib.unc.edu www-thieme-connect-com.libproxy.lib.unc.edu
-
c.706G>C
Case#: 46
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 4% (Moderate Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.706G>C (p.Gly236Arg)
ClinVar: NA
CAID: CA414441294
gnomAD: Not reported
-
c.3637dupA
Case#: 18
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1% (Severe Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, Possibility that sample was blinded for NGS and validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.3637dup (p.Ile1213AsnfsTer28)
ClinVar: NA
CAID: CA10568191
gnomAD: MAF for p.Ile1213AsnfsTer28 in the Other population 0.0002480<br>https://gnomad.broadinstitute.org/variant/X-154158427-A-AT
-
c.1372C>T
Case#: 12
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 28% (Mild Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3:c.1372C>T (p.Arg458Cys)
ClinVar: NA
CAID: CA414914682
gnomAD: Not reported
-
c.1336C>T
Case#: 8, Female HA carrier
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 80% (Severe Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.1336C>T (p.Arg446Ter)
ClinVar: 10145 https://www.ncbi.nlm.nih.gov/clinvar/variation/10145/
CAID: CA255038
gnomAD: Not reported
-
c.95T>C
Case#: 39
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 19% (Mild Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3:c.95T>C (p.Leu32Pro)
ClinVar: NA
CAID: CA414435358
gnomAD: Not reported
-
c.2945dupA
Case#: 17
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C <1% (Severe Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, Possibility that sample was blinded for NGS and validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.2945dup (p.Asn982LysfsTer9)
ClinVar: 10249 https://www.ncbi.nlm.nih.gov/clinvar/variation/10249/
CAID: CA255142
gnomAD: Not reported
-
c.6623A>G
Case#: 34
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 23%, Mild Phenotype, No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.6623A>G (p.Gln2208Arg)
ClinVar: 368117 https://www.ncbi.nlm.nih.gov/clinvar/variation/368117/
CAID: CA10567784
gnomAD: MAF for Gln2208Arg in the European (non-Finnish) population 0.00004320<br>https://gnomad.broadinstitute.org/variant/X-154090093-T-C?dataset=gnomad_r2_1
-
c.1345C>T
Case#: 43
DiseaseAssertion: Hemophilia B
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FIX:C 30% (Mild Phenotype)
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F9
Variant: NM_000133.3(F9):c.1345C>T (p.Arg449Trp)
ClinVar: 626990 https://www.ncbi.nlm.nih.gov/clinvar/variation/626990/
CAID: CA10529890
gnomAD: MAF for Arg449Trp in the European (non-Finnish) population 0.00006494<br>https://gnomad.broadinstitute.org/variant/X-138644189-C-T?dataset=gnomad_r2_1
-
c.575T>C
Case#: 5
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVIII:C 26% (Mild Phenotype), No inhibitors present
CasePreviousTesting: Screened for IVS-22 and IVS-1, sample was blinded for NGS and the sequencing component was validated by comparing results with Sanger Sequencing
Gene: F8
Variant: NM_000132.3(F8):c.575T>C (p.Ile192Thr)
ClinVar: 618637 https://www.ncbi.nlm.nih.gov/clinvar/variation/618637/
CAID: CA414919417
gnomAD: Not reported
Tags
- ClinVarID:626990
- inferred_gene_source:hgnc_tag
- FVIIItesting:Partial
- FIXtesting:Partial
- CAID:CA255142
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- Zygosity:NoZygosityAssertion
- Mutation:Missense
- Mutation:Frameshift
- ParentalTest:Unknown
- CaseInfo
- CAID:CA255038
- ClinVarID:10145
- CAID:CA10567784
- CAID:CA414441294
- CAID:CA414914682
- InheritancePattern:NoInheritanceAssertion
- DiseaseEntity:FactorIXDeficiency
- CAID:CA10568191
- CAID:CA10529890
- Gene:F9
- ClinVarID:10249
- HGNC:3551
- ClinVarID:368117
- Gene:F8
- CAID:CA414919417
- Mutation:Nonsense
- CAID:CA414435358
- inferred_gene_hgnc:3546
- inferred_gene_hgnc:3551
- HGNC:3546
Annotators
URL
-
-
onlinelibrary-wiley-com.libproxy.lib.unc.edu onlinelibrary-wiley-com.libproxy.lib.unc.edu
-
Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954 → Leu substitution in the factor VIII A3 domain D. M. Keeling, Oxford Haemophilia Centre, The Churchill Hospital, Oxford,Search for more papers by this authorK. Sukhu, Oxford Haemophilia Centre, The Churchill Hospital, Oxford,Search for more papers by this authorG. Kemball-Cook, Haemostasis Research Group, MRC Clinical Sciences Centre, Hammersmith Hospital, London,Search for more papers by this authorN. Waseem, Division of Medical and Molecular Genetics, Guy's and St Thomas's Medical School, London, U.K.,Search for more papers by this authorR. Bagnall, Division of Medical and Molecular Genetics, Guy's and St Thomas's Medical School, London, U.K.,Search for more papers by this authorJ. V. Lloyd, Haematology Division, Institute of Medical and Veterinary Science, Adelaide, AustraliaSearch for more papers by this author
PMID: 10554831
Gene: F8
HGNCID: 3546
-
-
onlinelibrary.wiley.com onlinelibrary.wiley.com
-
141
Case#: 141, male, 59 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.dup exons2_18, NM_000132.3:c.dup exons23_26
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
4
Case#: 4, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.741G>A
LegacyVariant:
ClinVar: No
CAID: CA414919022
gnomAD:
-
125
Case#: 125, male, 20 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.579_582dup
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
137
Case#: 137, male, 23 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 2.7%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.dup exon15
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
77
Case#: 77, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5552G>A
LegacyVariant:
ClinVar: No
CAID: CA414908513
gnomAD:
-
63
Case#: 63, male, 33 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.8%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2129G>T
LegacyVariant:
ClinVar: No
CAID: CA414904140
gnomAD:
-
66
Case#: 66, male, 16 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 11.8%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2167G>A
LegacyVariant:
ClinVar: 10246
CAID: CA255138
gnomAD:
-
15
Case#: 15, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.2275A>T
LegacyVariant:
ClinVar: No
CAID: CA414902563
gnomAD:
-
148
Case#: 148, male, 8 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1282_1298delAGTCAATATTTGAACAA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
154
Case#: 154, male, 27 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 4.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.3413delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
43
Case#: 43, male, 22 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.902G>A
LegacyVariant:
ClinVar: 10192
CAID: CA255079
gnomAD:
-
177
Case#: 177, male, 41 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons7_11
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
47
Case#: 47, male, 19 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1241A>G
LegacyVariant:
ClinVar: No
CAID: CA414915839
gnomAD:
-
90
Case#: 90, male, 12 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6406G>A
LegacyVariant:
ClinVar: No
CAID: CA414899430
gnomAD:
-
159
Case#: 159, male, 11 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 12%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
-
85
Case#: 85, male, 31 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 9%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6103G>A
LegacyVariant:
ClinVar: 381561
CAID: CA16609159
gnomAD:
-
49
Case#: 49, male, 56 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 5.1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1660A>C
LegacyVariant:
ClinVar: No
CAID: CA414911810
gnomAD:
-
168
Case#: 168, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.6%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5480delA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
105
Case#: 105, male, 8 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 49%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6683G>A
LegacyVariant:
ClinVar: 10098
CAID: CA255016
gnomAD:
-
98
Case#: 98, male, 31 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.7%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6544C>T
LegacyVariant:
ClinVar: 10321
CAID: CA255214
gnomAD:
-
172
Case#: 172, male, 32 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.del exons1_25
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
163
Case#: 163, male, 30 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.3931_3932delinsTTT
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
58
Case#: 58, male, 8 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.1909A>G
LegacyVariant:
ClinVar: No
CAID: CA414909856
gnomAD:
-
91
Case#: 91, male, 7 years old, Chinese
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 22%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.6437T>C
LegacyVariant:
ClinVar: 627110
CAID: CA414908033
gnomAD:
-
129
Case#: 129, male, 20 years old, Chinese
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.3637dupA
LegacyVariant:
ClinVar: No
CAID: CA10568191
gnomAD:
-
118
Case#: 118, male, 55 years old, Chinese
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: Noted Family History
ParentalTesting: Maternity confirmed
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 1.3%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: F8 gene variants were identified using next-generation sequencing (NGS), inverse shifting PCR and MLPA
Gene: F8
Variant: NM_000132.3:c.5219+3A>G
LegacyVariant:
ClinVar: No
CAID: CA873340051
gnomAD:
Tags
- ClinVarID:10246
- ToCheck
- CAID:CA414911810
- inferred_gene_source:hgnc_tag
- CAID:CA255146
- DiseaseSeverity:MildHemophiliaA
- FIXtesting:Partial
- Mutation:Splice
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- DiseaseSeverity:SevereHemophiliaA
- Mutation:Missense
- Mutation:Frameshift
- ClinVarID:10192
- CAID:CA414908513
- ClinVarID:381561
- CaseInfo
- CAID:CA414908033
- CAID:CA255214
- CAID:CA414902563
- CAID:CA414909856
- CAID:CA414919022
- UnregisteredVariant
- Zygosity:Hemizygous
- CAID:CA255016
- ClinVarID:627110
- CAID:CA10568191
- ClinVarID:10098
- Mutation:Large
- CAID:CA414915839
- CAID:CA16609159
- ClinVarID:10321
- Inhibitor:Absent
- Gene:F8
- CAID:CA414904140
- CAID:CA873340051
- AssayDiscrepancy:NotReported
- CAID:CA255079
- CAID:CA414899430
- SupplementalData
- Inhibitor:Present
- Mutation:Nonsense
- inferred_gene_hgnc:3546
- DiseaseSeverity:ModerateHemophiliaA
- MultipleGeneVariants
- CAID:CA255138
- ParentalConfirmation:Maternity
- HGNC:3546
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
S18
Case#: S18, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S28
Case#: S28, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125, HP:0005261
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA, Testis bleeding
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.del exon15
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
S10
Case#: S10, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NM_000132.3:c.1931T>G
LegacyVariant:
ClinVar: No
CAID: CA414909677
gnomAD:
-
S6
Case#: S6, Iranian
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Mucosal bleeding, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The F8 gene was directly sequenced for all 26 exons using the Sanger sequencing method. PCR was performed and subsequently analyzed
Gene: F8
Variant: NA
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
Mutation detection and inhibitor risk in Iranian patients with Hemophilia A: Six novel mutations
PMID: 33363863
Gene: F8
HGNCID: 3546
Tags
- ToCheck
- UnregisteredVariant
- inferred_gene_source:hgnc_tag
- FVIIItesting:Partial
- CAID:CA414909677
- Mutation:Large
- DiseaseSeverity:SevereHemophiliaA
- ClinGen Coag Fac Def VCEP
- DiseaseEntity:FactorVIIIDeficiency
- Inhibitor:Absent
- Gene:F8
- AssayDiscrepancy:NotReported
- Mutation:Missense
- Inhibitor:Present
- ParentalTest:Unknown
- CaseInfo
- General
- inferred_gene_hgnc:3546
- Mutation:Intronic
- HGNC:3546
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
c.5508_5521del
Case#: 7
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.5508_5521del (p.Trp1836Ter)
ClinVar: NA
CAID: CA1139532049
gnomAD: Not reported
-
c.839G>A
Case#: 17, Spanish
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Mild
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.839G>A (p.Gly261Asp)
ClinVar: NA
CAID: CA414918260
gnomAD: Not reported
-
c.4155_4195dup
Case#: 6
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Severe, Inhibitors present
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.4157_4197dup (p.Pro1400SerfsTer38)
ClinVar: NA
CAID: CA1139532048
gnomAD: Not reported
-
c.782T>C
Case#: 16, Spanish
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: Moderate
CasePreviousTesting: All 26 exons and exon-intron boundaries of the F8 gene were amplified using primers and PCR, analyzed by direct forward and reverse sequencing using a DNA sequencing kit
Gene: F8
Variant: NM_000132.3:c.782T>C (p.Leu242Pro)
ClinVar: NA
CAID: CA414918925
gnomAD: Not reported
Tags
- UnregisteredVariant
- CAID:CA414918925
- inferred_gene_source:hgnc_tag
- CAID:CA414918260
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- Gene:F8
- Zygosity:NoZygosityAssertion
- Mutation:Missense
- Mutation:Frameshift
- ParentalTest:Unknown
- CaseInfo
- inferred_gene_hgnc:3546
- InheritancePattern:NoInheritanceAssertion
- HGNC:3546
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
UQU-HA39
Case#: UQU-HA39, Male, 1-months-old, Saudi Arabia
DiseaseAssertion: Hemophilia A
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0001892 (Abnormal bleeding)
CaseHPOFreeText: Moderate, FVIII: 5-40% (moderate HA) based on text
CasePreviousTesting: Screened for inversion 22 by inverse PCR, screened for inversion 1 by multiplexed PCR, capillary sequencing (Sanger method) was performed for factor VIII all 26 exons
Gene: F8
Variant: NM_000132.3:c.2138del (p.Asn713ThrfsTer9)
ClinVar: NA
CAID: CA1139532050
gnomAD: Not reported
Tags
- Zygosity:NoZygosityAssertion
- Mutation:Frameshift
- inferred_gene_source:hgnc_tag
- FVIIItesting:Partial
- ParentalTest:Unknown
- CaseInfo
- CAID:CA1139532050
- inferred_gene_hgnc:3546
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- Gene:F8
- InheritancePattern:NoInheritanceAssertion
- HGNC:3546
Annotators
URL
-
-
www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
-
B77. B78
Case#: B77, B78
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 13, FVIII:AG = 8, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.6358T>C, NM_000132.4:c.6360T>A, NM_000132.4:c.6360T>G
LegacyVariant:
ClinVar: No
CAID: CA414899758, CA414899736, CA255202
gnomAD:
-
A13
Case#: A13
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 10, FVIII:AG = 60, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.5303G>A
LegacyVariant:
ClinVar: No
CAID: CA10568007
gnomAD:
-
B14 – B16
Case#: B14 - B16
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 10, FVIII:AG = 18, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.1293G>C, NM_000132.4:c.1293G>T
LegacyVariant:
ClinVar: No
CAID: CA414915298, CA255100
gnomAD:
-
B32 – B44
Case#: B32 - B44
DiseaseAssertion: NA
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C Chr = 94, FVIII:AG = 88, inverse assay discrepancy present (OSA<CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.2215G>A
LegacyVariant:
ClinVar: No
CAID: CA255139
gnomAD:
-
A5 – A8
Case#: A5 - A8
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C = 26, FVIII:AG = 60, assay discrepancy present (OSA>CSA)
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: Coding region and intron/exon bound-aries of the F8 gene were amplified from all patient samples and directly sequenced using primers
Gene: F8
Variant: NM_000132.4:c.1649G>A
LegacyVariant:
ClinVar: No
CAID: CA255115
gnomAD:
Tags
- ToCheck
- PreviousTesting:None
- inferred_gene_source:hgnc_tag
- DiseaseSeverity:MildHemophiliaA
- AssayDiscrepancy:OSA<CSA
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- NoDiseaseAssertion
- CAID:CA255115
- Zygosity:NoZygosityAssertion
- Mutation:Missense
- ParentalTest:Unknown
- CaseInfo
- Inhibitor:NotReported
- InheritancePattern:NoInheritanceAssertion
- FVIIItesting:Full
- CAID:CA10568007
- Gene:F8
- AssayDiscrepancy:OSA>CSA
- CAID:CA255139
- inferred_gene_hgnc:3546
- MultipleGeneVariants
- HGNC:3546
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
Assessment of the F9 genotype-specific FIX inhibitor risks and characterization of 10 novel severe F9 defects in the first molecular series of Argentine patients with haemophilia B
PMID: 23093250
Gene: F9
HGNCID: 3551
-
-
www-thieme-connect-de.libproxy.lib.unc.edu www-thieme-connect-de.libproxy.lib.unc.edu
-
091–2011
Case#: 091-2011
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5393C>A
LegacyVariant:
ClinVar: No
CAID: CA414909064
gnomAD:
-
084–2005
Case#: 084-2005
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1910A>G
LegacyVariant:
ClinVar: No
CAID: CA414909849
gnomAD:
-
020–2071
Case#: 020-2071
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1492G>A
LegacyVariant:
ClinVar: No
CAID: CA255109
gnomAD:
-
066–2002
Case#: 066-2002
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5399G>A
LegacyVariant:
ClinVar: No
CAID: CA255162
gnomAD:
-
071–2025
Case#: 071-2025
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.2167G>A
LegacyVariant:
ClinVar: No
CAID: CA255138
gnomAD:
-
020–2070
Case#: 020-2070
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.558C>G
LegacyVariant:
ClinVar: No
CAID: CA414919454
gnomAD:
-
003–2002
Case#: 003-2002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
-
020–1003
Case#: 020-1003
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
035–2020
Case#: 035-2020
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.5275G>A
LegacyVariant:
ClinVar: No
CAID: CA414911087
gnomAD:
-
020–2021
Case#: 020-2021
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1396T>C
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
071–2037
Case#: 071-2037
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
-
022–2003
Case#: 022-2003
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.278C>T
LegacyVariant:
ClinVar: No
CAID: CA414920106
gnomAD:
-
003–2025
Case#: 003-2025
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID:
gnomAD:
-
001–1010
Case#: 001-1010
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.3274_3276delAACinsCC
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
035–2016
Case#: 035-2016
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
-
005–1002
Case#: 005-1002
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant:
LegacyVariant:
ClinVar: No
CAID: No
gnomAD:
-
084–2003
Case#: 084-2003
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%, Inhibitor present
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.209_212delTTGT
LegacyVariant:
ClinVar: No
CAID: CA255050
gnomAD:
-
020–2065
Case#: 020-2065
DiseaseAssertion: Hemophilia A, mild
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 5% < FVIII:C < 40%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1834C>T
LegacyVariant:
ClinVar: No
CAID: CA255129
gnomAD:
-
004–2019
Case#: 004-2019
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.3637delA
LegacyVariant:
ClinVar: No
CAID: CA255146
gnomAD:
-
060–2006
Case#: 060-2006
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.1618C>A
LegacyVariant:
ClinVar: No
CAID: CA414911950
gnomAD:
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001–2026
Case#: 001-2026
DiseaseAssertion: Hemophilia A, severe
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: FVIII:C < 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.986G>A
LegacyVariant:
ClinVar: No
CAID: CA255089
gnomAD:
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047–2002
Case#: 047-2002
DiseaseAssertion: Hemophilia A, moderate
FamilyInfo: NA
ParentalTesting: NA
CasePresentingHPOs: HP:0003125
CaseHPOFreeText: 1% < FVIII:C < 5%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: The 26 exons and their flanking regions of F8 were amplified by PCR using specific primers with a simple modification
Gene: F8
Variant: NM_000132.3:c.6011C>A
LegacyVariant:
ClinVar: No
CAID: CA414905140
gnomAD:
Tags
- ToCheck
- PreviousTesting:None
- inferred_gene_source:hgnc_tag
- FVIIItesting:Partial
- DiseaseSeverity:MildHemophiliaA
- CAID:CA255146
- FIXtesting:Partial
- DiseaseSeverity:SevereHemophiliaA
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- CAID:CA414905140
- Zygosity:NoZygosityAssertion
- Mutation:InframeDelins
- Mutation:Missense
- ParentalTest:Unknown
- CaseInfo
- CAID:CA255162
- CAID:CA414911950
- Inhibitor:NotReported
- InheritancePattern:NoInheritanceAssertion
- CAID:CA255050
- CAID:CA255089
- UnregisteredVariant
- CAID:CA414919454
- Mutation:Large
- Inhibitor:Absent
- Gene:F8
- AssayDiscrepancy:NotReported
- CAID:CA414909849
- CAID:CA255109
- CAID:CA414911087
- SupplementalData
- Inhibitor:Present
- CAID:CA255129
- CAID:CA414909064
- inferred_gene_hgnc:3546
- DiseaseSeverity:ModerateHemophiliaA
- CAID:CA414920106
- CAID:CA255138
- HGNC:3546
Annotators
URL
-
-
oce-ovid-com.libproxy.lib.unc.edu oce-ovid-com.libproxy.lib.unc.edu
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Table 2
Case#: Cz35, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 2
Case#: Cz25, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Sporadic
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C 4%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: NM_000132.3:c.1538-18G>A
ClinVar: 811357 https://www.ncbi.nlm.nih.gov/clinvar/variation/811357/
CAID: CA873354114
gnomAD: Not reported
-
Table 1
Case#: Cz32, Italy (Calabria)
DiseaseAssertion: Hemophilia A
FamilyInfo: Inherited
ParentalTesting: NA
CasePresentingHPOs: NA
CaseHPOFreeText: FVII:C <1%
CasePreviousTesting: Polymerase chain reaction (PCR) analysis, Long PCR for detecting the intron 22 inversion was performed, Direct cycle sequence analysis using the Taq dye-deoxy terminator method
Gene: F8
Variant: F8, IVS22 INV
ClinVar: 10150 https://www.ncbi.nlm.nih.gov/clinvar/variation/10150/
CAID: NA
gnomAD: Not reported
Tags
- inferred_gene_source:hgnc_tag
- FVIIItesting:Partial
- InheritancePattern:Xlinked
- DiseaseEntity:FactorVIIIDeficiency
- ClinGen Coag Fac Def VCEP
- Gene:F8
- ClinVarID:10150
- Zygosity:NoZygosityAssertion
- CAID:CA873354114
- ParentalTest:Unknown
- CaseInfo
- ClinVarID:811357
- inferred_gene_hgnc:3546
- Mutation:Intronic
- InheritancePattern:DeNovoAssertion
- HGNC:3546
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
PMID: 30160169
Gene: F8
HGNC: 3546
NoEvidence: This article does not mention probands with variants in Hemophilia A
-
-
journals.lww.com journals.lww.com
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The proband, 12-year-old boy with moderate bleeding history, had manifest prolonged activated partial thromboplastin time (98.1 s) and markedly decreased FIX activity (1%).
Case#: 12 year old male
DiseaseAssertion: Hemophilia B, moderate
FamilyInfo: Uncle had mild Hemophilia B
ParentalTesting: No
CasePresentingHPOs: HP:0011858
CaseHPOFreeText: FIX:C = 1%
CaseNotHPOs: NA
CaseNotHPOFreeText: NA
CasePreviousTesting: exons and introns were amplified by PCR and subsequently analyzed by direct sequencing
Gene: F9
Variant:
LegacyVariant:
ClinVar:
CAID:
gnomAD:
Tags
- DiseaseEntity:FactorIXDeficiency
- FIXtesting:Full
- Zygosity:Hemizygous
- PreviousTesting:None
- FamilyInfo
- inferred_gene_source:hgnc_tag
- ClinGen Coag Fac Def VCEP
- ParentalTest:Unknown
- DiseaseSeverity:ModerateHemophiliaB
- CaseInfo
- InheritancePattern:Xlinked
- HGNC:3551
- inferred_gene_hgnc:3551
- Gene:F9
Annotators
URL
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Haemophilia A: the consequences of de novo mutations. Two case reports
PMID: 28488976
Gene: F8
HGNCID: 3546
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-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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6 months of age, the proband (male, born on 20 February 2008)
Case2: 6-month-old Male, China
DiseaseAssertion: Hemophilia B (Factor IX-deficient)
FamilyInfo: Mother and maternal grandmother are HB carriers due to a novel mutation in intron 3. Pedigree shown in Figure 1.
ParentalTesting: The F9 exons were amplified (RT-PCR) and exons 1 to 8 of the F9 gene were analyzed with the ABI 3130 Genetic Analyzer, Sequenced intron 3 of the F9 gene
CasePresentingHPOs: HP:0011858 (Reduced factor IX activity)
CaseHPOFreeRext: FIX:C 1%, Pelioma, Cyanotic bumps, Subcutaneous bleeding, knee swelling from crawling
CasePreviousTesting: Prenatal testing at 20 weeks
Gene: F9
Variant: NM_000133.3(F9):c.278-3A>G
ClinVar: 92225 https://www.ncbi.nlm.nih.gov/clinvar/variation/92225/#id_first
CAID: CA285284
gnomAD: Not Reported
Tags
- Zygosity:NoZygosityAssertion
- DiseaseEntity:FactorIXDeficiency
- CAID:CA285284
- ParentalTest:Both
- FamilyInfo
- inferred_gene_source:hgnc_tag
- ClinGen Coag Fac Def VCEP
- FIXtesting:Partial
- CaseInfo
- InheritancePattern:Xlinked
- HGNC:3551
- inferred_gene_hgnc:3551
- Mutation:Intronic
- ClinVarID:92225
- Gene:F9
Annotators
URL
-
-
link.springer.com link.springer.com
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c.2545 A > G (p.T849A) was observed in family 087
Case#: Jiang_2015_Family_087_Patient_III:2, male, age 28 at time of report, national origin listed as Chinese
CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0025573 (Mild myopia), HP:0032037 (Mildly reduced visual acuity), HP:0007703 (Abnormality of retinal pigmentation), HP:0008275 (Abnormal light-adapted electroretinogram), HP:0000642 (Red-green dyschromatopsia)
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0000662 (Nyctalopia), HP:0000639 (Nystagmus)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing included mapping the disease locus in this family to the region of chr17p13.1-2 containing AIPL1, PITPNM3, and GUCY2D (PMID: 23734073).
CaseMethod1: Sanger sequencing of PCR products from all exons and flanking regions of the GUCY2D, AIPL1, and PITPNM3 loci.
CaseMethod2: Allele-specific PCR analysis to genotype the proband and family members
CaseGenotypingMethod: The proband was genotyped by linkage mapping of the phenotype within affected and unaffected members of his family, followed by Sanger sequencing of PCR products from all exons and flanking regions of the 3 candidate loci, and finally allele-specific PCR analysis to genotype the proband and family members.
Variant: The proband harbors the NM_000180.4(GUCY2D)):c.2545A>G (p.Thr849Ala) variant in the heterozygous state.
CAID: CA397953755
gnomAD: The variant was not found in gnomAD.
VariantEvidence: NM_000180.4(GUCY2D)):c.2545A>G (p.Thr849Ala) is a missense variant located within the coiled-coil domain that mediates dimerization. Missense variants at the nearby Codon 838 have proven to constitute a hot spot disrupted in other families similarly affected with autosomal dominant cone-rod dystrophy (PMID: 11115851, PMID: 12552567, PMID: 26298565). Cases from this family appear to be less severely affected than those.
CaseAddInfo: The proband has two older family members who are similarly affected and who harbor the variant.
CasePMIDs: PMID: 23734073
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Genotype-phenotype correlation in British families with X linked congenital stationary night blindness
PMID: 14609846
Gene: NYX
HGNC: 8082
Disease: Congenital stationary night blindness 1A
MONDO: 0010690
InheritancePattern: X-linked recessive
Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.
Penetrance: Penetrance is thought to be complete.
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nonsense mutation found in family X08
Case#: Allen_2003_Familly_X08_Proband, male, age not mentioned, British national origin
CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)
CaseHPOFreeText: ERG with absent scotopic oscillatory potential, subnormal ON response
CaseNotHPOs: N/A
CaseNotHPOFreeText: Normal OFF response
CasePreviousTesting: N/A
CaseMethod1: Sanger sequencing of PCR-amplified exons from NYX and CACNA1F
CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus
CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by microsatellite-based haplotype analysis of families sharing the same variant.
Variant: The proband harbors the NM_022567.2(NYX):c.895C>T (p.Gln299Ter) variant on the X chromosome.
CAID: CA412991558
gnomAD: NM_022567.2(NYX):c.895C>T (p.Gln299Ter) was not found in gnomAD.
VariantEvidence: NM_022567.2(NYX):c.895C>T (p.Gln299Ter) is a nonsense variant in exon 3/3 that is not predicted to trigger NMD but truncates the C-terminal 38% of the protein product. A separate publication (PMID: 14507859) indicates that variants (such as this one) that remove the C-terminal GPI anchor disrupt NYX function by triggering its mislocalization to and accumulation in the ER and Golgi and its absence from its normal destination at the cell surface.
CaseAddInfo: N/A
CasePMIDs: N/A
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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missense
Case#: Mykykyn_2002_Proband_PR1-1, gender not specified, age not described, family origin reported as from Puerto Rico
CasePresentingHPOs: N/A
CaseHPOFreeText: The proband has been previously diagnosed with Bardet-Biedl syndrome based on at least three of the following features; obesity, polydactyly, renal anomalies, retinopathy, hypogonadism, and/or mental retardation.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: The proband and their affected and unaffected family members were subjected to mapping of the disease-associated locus to chromosome 11, followed by PCR- and Sanger sequencing-based genotyping of chromosome 11 markers.
CaseMethod1: linkage mapping
CaseMethod2: Sanger sequencing of BBS1
CaseGenotypingMethod: The proband and their affected and unaffected family members were subjected to linkage mapping of the disease-associated locus to chromosome 11, followed by PCR- and Sanger sequencing-based genotyping of chromosome 11 markers. Sanger sequencing of BBS1 was subsequently used to identify the variant.
Variant: The proband harbors the NM_024649.5(BBS1):c.1169T>G (p.Met390Arg) variant in the homozygous state.
ClinVar ID: 12143
gnomAD: The variant is found in gnomAD v2.1.1 at a frequency of 0.002773 in the European (non-Finnish) population, with 358 alleles / 129114 total alleles (0 homozygotes) https://gnomad.broadinstitute.org/variant/11-66293652-T-G?dataset=gnomad_r2_1
VariantEvidence: NM_024649.5(BBS1):c.1169T>G (p.Met390Arg) is a missense variant with mouse knock-in evidence of a similar disease-causing effect in the homozygous state (PMID: 18032602). This has not been taken into account in scoring, as the mouse model has been scored separately. However, it has provided a rationale not to down-score for the relatively high gnomAD frequency of this variant.
CaseAddInfo: The proband's family is described as consanguineous.
CasePMIDs: N/A
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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15 year old boy (patient II‐1)
Case#: Moore_2006_Family_1_Patient_II-1, male, 15 years old at time of report, national origin not mentioned
CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0011109 (Chronic sinusitis), HP:0031353 (Otitis media with effusion), HP:0002837 (Recurrent bronchitis), HP:0100750 (Atelectasis), HP:0002110 (Bronchiectasis), HP:0006536 (Airway obstruction), HP:0005101 (High-frequency hearing impairment), HP:0012263 (Immotile cilia), HP:0012258 (Abnormal axonemal organization of respiratory motile cilia), HP:0012264 (Absent central microtubular pair morphology of respiratory motile cilia), HP:0012256 (Absent outer dynein arms), HP:0012257 (Absent inner dynein arms)
CaseHPOFreeText: The patient received a diagnosis of primary ciliary dyskinesia in early childhood, followed by retinitis pigmentosa diagnosed later in childhood. Atelectasis was severe and led to partial lobectomy at age 14 years. Microbiology detected Haemophilus influenzae. Biopsies showed both motile and immotile cilia.
CaseNotHPOs: HP:0002643 (Neonatal respiratory distress), HP:0012418 (Hypoxemia), HP:0030853 (Heterotaxy)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Based on a family history consistent with X-linked inheritance, the patient and family members were subjected to segregation analysis using 4 microsatellite markers on the X chromosome. Genome-wide methods were not used for genotyping.
CaseMethod1: Sanger sequencing of PCR products from each of the 19 coding exons of RPGR, including the flanking intronic sequences
CaseMethod2: N/A
CaseGenotypingMethod: The patient and family members were subjected to segregation analysis using 4 microsatellite markers on the X chromosome. Sanger sequencing of PCR products from each of the 19 coding exons of RPGR, including the flanking intronic sequences, was then performed. Genome-wide methods were not used for genotyping.
Variant: The patient harbors the NM_001034853.2(RPGR):c.572_619+9del variant in the hemizygous state.
CAID: CA2573131867
gnomAD: This variant was not found in gnomAD v.2.1.1.
VariantEvidence: NM_001034853.2(RPGR):c.572_619+9del is a deletion variant spanning the function between exon 6 and intron 6. It has been shown to yield a shorter mRNA generated by the use of a cryptic splice donor site in exon 6 (Figure 4) that is predicted to trigger a frameshift and nonsense-mediated decay or disruption of the C-terminal 84% of the protein product.
CaseAddInfo: The proband is a member of Family 1, which has a pedigree shown in Figure 1. The patient's family includes a similarly affected brother and a mother diagnosed with retinitis pigmentosa, both harboring the RPGR variant of interest. Parents are reportedly non-consanguineous.
CasePMIDs: N/A
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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A novel GPR143 duplication mutation in a Chinese family with X-linked congenital nystagmus
PMID: 19390656
Gene: GPR143
HGNC: 20145
Disease: X-linked recessive ocular albinism
MONDO: 0021019
InheritancePattern: X-linked recessive
Prevalence: Ocular albinism has an estimated prevalence between 1 in 111,000 and 1 in 1,000,000 live births (PMID: 35495622)
Penetrance: Fully penetrant in males, with onset in infancy. Most female carriers appear to be unaffected.
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In this study, we present a four-generation Chinese family with X-linked CN. All affected individuals exhibited nystagmus but without any typical signs of OA1. Upon genetic analysis, we characterized the underlying molecular defect as a novel 19 base pair (bp) duplication in exon 1 of GPR143, causing a frame-shift in all affected males.
Case#: Peng_2009_Patient_IV:3, male, age of onset not reported, family origin reported to be from China
CasePresentingHPOs: HP:0006934 (Congenital nystagmus)
CaseHPOFreeText: The proband has been diagnosed with congenital nystagmus, with family members showing an X-linked pattern of inheritance.
CaseNotHPOs: N/A
CaseNotHPOFreeText: The affected individuals are described as lacking the typical signs of ocular albinism 1, but details have not been described.
CasePreviousTesting: Genotyping was initially performed by linkage mapping using markers on the X chromosome.
CaseMethod1: linkage analysis
CaseMethod2: Sanger sequencing
CaseGenotypingMethod: Genotyping was initially performed by linkage mapping using markers on the X chromosome, followed by Sanger sequencing of PCR products from each exon of the GPR143 gene. Family members were subsequently genotyped by allele-specific PCR.
Variant: The proband harbors the NM_000273.3:c.291_309dup (p.Asp104PhefsTer3) variant in the hemizygous state.
CAID: CA2573320693
gnomAD: This variant was not found in gnomAD v2.1.1.
VariantEvidence: NM_000273.3:c.291_309dup (p.Asp104PhefsTer3) is a frameshift variant in exon 2 of 9, and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 75% of the protein product.
CaseAddInfo: The proband is from a family with at least three other affected males who also harbor the variant.
CasePMIDs: N/A
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iovs.arvojournals.org iovs.arvojournals.org
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Unique Variants in OPN1LW Cause Both Syndromic and Nonsyndromic X-Linked High Myopia Mapped to MYP1
PMID: 26114493
Gene: OPN1LW
HGNC: 9936
Disease: protan color blindness
MONDO: 0010565
InheritancePattern: X-linked
Prevalence: The overall prevalence of protan color blindness is approximately 1% in males, which is higher than that of blue cone monochromacy (~1 in 100,000, PMID: 35759666).
Penetrance: Known disease-causing alleles appear to be almost completely penetrant in males (PMID: 21167193).
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iovs.arvojournals.org iovs.arvojournals.org
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Identification of Novel RPGR ORF15 Mutations in X-linked Progressive Cone-Rod Dystrophy (XLCORD) Families
PMID: 15914600
Gene: RPGR
HGNC: 10295
Disease: RPGR-related retinopathy
MONDO: MONDO:0100437
InheritancePattern: X-linked
Prevalence: The prevalence of RPGR-related retinopathy is calculated to be approximately 1 in 214,000, based on the known incidence of retinitis pigmentosa at 1 in 3,000, the proportion of retinitis pigmentposa that is X-linked at 20%, and the proportion of X-linked retinitis pigmentosa that is RPGR-associated at 70% (PMID: 34985506).
Penetrance: Penetrance is nearly 100% in hemizygous males but is incomplete and dependent upon the variant in heterozygous female carriers.
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www.nature.com www.nature.com
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The A187K mutation was found in three families from Sweden sharing a common haplotype.
Case#: Pusch_2000_Family_9069_proband, male, 18 years of age, Swedish family origin
CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)
CaseHPOFreeText: ERG with absent oscillatory-potential wavelets
CaseNotHPOs: HP:0001098 (Abnormal fundus morphology), HP:0030473 (Abnormal light-adapted flicker electroretinogram)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP.
CaseMethod1: Sanger sequencing of PCR amplified exons from NYX
CaseMethod2: N/A
CaseGenotypingMethod: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP. This was followed by Sanger sequencing of PCR products to identify the variant.
Variant: The proband harbors the NM_022567.2(NYX):c.559_560delinsAA (p.Ala187Lys) variant in his X-chromosome.
ClinVar: 11423
gnomAD: NM_022567.2(NYX):c.559_560delinsAA (p.Ala187Lys) was not found in gnomAD.
VariantEvidence: This is missense variant does not have experimental evidence of impact on the protein product, but is a recurrent variant observed in this paper in multiple Swedish families (2996, 9069, and 2999) with a shared haplotype.
CaseAddInfo: Phenotype information is found in PMID: 12397430.
CasePMIDs: 12397430
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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In contrast, at P12, retinal sections of C57BL/6J-Pde6anmf363/nmf363 mutants and controls are indistinguishable (Fig. 2C and D). By P14, an ∼30% reduction in ONL thickness is observed in mutant mice. The thickness of the IS and OS is almost comparable to that of C57BL/6J-Pde6anmf363/+ controls until P16. Degeneration of OS is clearly seen in C57BL/6J-Pde6anmf363/nmf363 mutants at P19. However, even at P36, a single layer of cell bodies still remained in the ONL of the mutant mice. Therefore, the photoreceptor degeneration while rapid has a later onset and is prolonged in C57BL/6J-Pde6anmf363/nmf363 mutants compared to A.B6-Tyr+/J-Pde6anmf282/nmf282 mutant mice. Functional analyses by ERG are consistent with these histological observations (Fig. 2E). While the ERG response is extinguished in A.B6-Tyr+/J-Pde6anmf282/nmf282 mutants at P14, some residual activity is still observed in C57BL/6J-Pde6anmf363/nmf363 mutants at P21.
ExperimentName: Murine model of PDE6A loss-of-function (Pde6Anmf363/nmf363)
NonHumanModel: Mus musculus
GeneAlteration: Mice were found to develop retinal degeneration due to a homozygous missense variant (2159G>A) at codon 670 substituting glycine for aspartic acid.
ModelPhenotype: HP:0030609 (Photoreceptor layer loss on macular OCT), HP:0030478 (Abnormal amplitude of dark-adapted bright flash electroretinogram)
HumanPhenotype: HP:0011463 (Childhood onset), HP:0000662 (Nyctalopia), HP:0007994 (Peripheral visual field loss), HP:0000543 (Optic disc pallor), HP:0007843 (Attenuation of retinal blood vessels), HP:0007737 (Bone spicule pigmentation of the retina), HP:0000654 (Decreased light- and dark-adapted electroretinogram amplitude), HP:0007984 (Electronegative electroretinogram)
ModelEvidence: This mutation caused photoreceptor outer nuclear layer outer segment thinning (Figures 2C, 2D, 7), decreased dark-adapted bright flash ERG amplitude (Figure 2E), and decreased cGMP/PDE activity (Figure 3C).
ModelVariant: The model does not harbor a variant equivalent to one from the human patients, but rather has a mutagenesis-induced missense variant disrupting Pde6a leading to partial loss-of-function.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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mice with a targeted disruption of Lrp5 develop a low bone mass phenotype. In vivo and in vitro analyses indicate that this phenotype becomes evident postnatally, and demonstrate that it is secondary to decreased osteoblast proliferation and function in a Cbfa1-independent manner. Lrp5 is expressed in osteoblasts and is required for optimal Wnt signaling in osteoblasts. In addition, Lrp5-deficient mice display persistent embryonic eye vascularization due to a failure of macrophage-induced endothelial cell apoptosis. These results implicate Wnt proteins in the postnatal control of vascular regression and bone formation, two functions affected in many diseases. Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation.
ExperimentName: Targeted disruption of Lrp5 in mice
NonHumanModel: Mus musculus
GeneAlteration: Model animals were subjected to targeted disruption of Lrp5 by inserting an IRES-LacZ-Neomycin cassette to replace the region encoding the extracellar domain, starting at amino acid 373.
ModelPhenotype: HP:0004349 (Reduced bone mineral density), HP:0410280 (Pediatric onset), decreased osteoblast proliferation, HP:0007968 (Remnants of the hyaloid vascular system), failure of macrophage-mediated endothelial cell apoptosis
HumanPhenotype: HP:0000939 (Osteoporosis), HP:0011463 (Childhood onset), HP:0000541 (Retinal detachment), HP:0007968 (Remnants of the hyaloid vascular system), HP:0008046 (Abnormal retinal vascular morphology), HP:0000618 (Blindness), HP:0001249 (Intellectual disability), HP:0020110 (Bone fracture), HP:0000938 (Osteopenia), HP:0000926 (Platyspondyly)
ModelEvidence: Model animals subjected to targeted disruption of Lrp5 resembled human patients in that they exhibited reduced bone mineral density in the post-natal stage (Figs. S2, 3A), decreased osteoblast proliferation (Fig. 4), delayed ossification (Fig. 5), and remnants of the hyaloid vascular system due to failure of macrophage-mediated endothelial cell apoptosis (Fig. 8).
ModelVariant: The model features disruption of the wild-type Lrp5 gene, but not a mutation equivalent to a human variant.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Heterozygous 'null allele' mutation in the human peripherin/RDS gene
PMID: 8111389
Gene: PRPH2
HGNC: 9942
Disease: retinitis pigmentosa 7
MONDO: 0011974
InheritancePattern: semi-dominant
Prevalence: The incidence of PRPH2-related cases among inherited retinal dystrophies is reported to range from 3.5% in North America to 10.3% in France (PMID: 36010202).
Penetrance: The penetrance among biallelic cases appears to be complete, while the monoallelic cases exhibit incomplete penetrance (PMID: 36609934).
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Landscape of pathogenic variants in six pre-mRNA processing factor genes for retinitis pigmentosa based on large in-house data sets and database comparisons
PMID: 35138024
Gene: PRPF4
HGNC: 17349
Disease: retinitis pigmentosa 70
MONDO: 0014400
InheritancePattern: autosomal dominant
Prevalence: The overall prevalence of retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,500 and 1 in 27,000). The proportion of that incidence made up by the specific form caused by variants in PRPF4 is not clear.
Penetrance: Known disease-causing alleles appear to be incompletely penetrant (PMID: 25383878).
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Mutations in the Genes for Interphotoreceptor Matrix Proteoglycans, IMPG1 and IMPG2, in Patients with Vitelliform Macular Lesions
PMID: 28644393
Gene: IMPG2
HGNC: 18362
Disease: retinitis pigmentosa 56
MONDO: 0013314
InheritancePattern: semi-dominant
Prevalence: Vitelliform macular dystrophy in general is estimated to have a prevalence of 1 in 5,500 (PMID: 27120116).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete, while heterozygous carriers of deleterious variants show incomplete penetrance and variable expressivity.
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Molecular cloning of a retina-specific membrane guanylyl cyclase
PMID: 1356371
Gene: GUCY2D
HGNC: 4689
Disease: Leber congenital amaurosis 1
MONDO: 0008764
InheritancePattern: Autosomal Recessive
Prevalence: The overall prevalence of Leber congenital amaurosis is between 1 in 33,000 and 1 in 100,000 newborns, while the proportion of Leber congenital amaurosis caused by GUCY2D variants is between 10% and 20% (PMID: 10951519). Thus, the prevalence of Leber congenital amaurosis 1 is between 1 in 165,000 and 1 in 1,000,000.
Penetrance: Fully penetrant, with onset in neonates or in infancy
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Like other membrane guanylyl cyclases, the 1101 aa retGC is predicted to have a hydrophobic amino-terminal signal sequence followed by a large extracelluiar domain, a single membrane spanning domain, a kinase homology domain, and a guanylyl cyclase catalytic domain. In contrast to other membrane guanylyl cylases, such as natriuretic peptide receptors, retGC has a relatively high basal level of activity when expressed in human 293 cells. cGMP production by retGC is unaffected by any of the known natriuretic peptides. In situ hybridization analysis of a variety of rhesus monkey tissues showed retGC transcripts to be localized exclusively along the retinal outer nuclear layer, corresponding to the nuclei of the rod and cone photoreceptor cells. Our results suggest that retGC may synthesize cGMP required for recovery of the dark state after phototransduction.
Selection B - Gene function is consistent with phenotype.
GOterm: GO:0007168 (receptor guanylyl cyclase signaling pathway)
FunctionalEvidence: Exogenous expression of the gene product in 293 cells exhibits a high level of cGMP production activity. When combined with the in situ hybridization evidence showing its expression along the retinal outer nuclear layer (coinciding with the rod and cone photoreceptor cell nuclei), this biochemical evidence indicates a function in synthesizing cGMP to promote recovery of the dark state following phototransduction.
FunctionalHPO: HP:0000662 (Nyctalopia), HP:0007663 (Reduced visual acuity), HP:0007688 (Undetectable light- and dark-adapted electroretinogram), HP:0007703 (Abnormality of retinal pigmentation)
PhenotypeEvidence: The ability of the exogenously expressed enzyme to efficiently catalyze cGMP production (Figure) is consistent with the loss of photoreceptor function that is characteristic of the disease, as abnormalities in cGMP levels have long been associated with photoreceptor degeneration (PMID: 4369896).
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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out-of-frame
Case#: Xin_Patient_4, sex not mentioned, age 12 at time of study, U.S. nationality, ethnicity listed as Hispanic
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing for mutations in the CLN1, CLN2, CLN3, CLN6, and CLN8 had already occurred, using PCR amplification and Sanger sequencing to exclude the possibility of variants in the exons and surrounding noncoding regions. Genome-wide analysis methods were not used, as NCL had already been diagnosed based on clinical phenotypes.
CaseMethod1: PCR amplification of the coding and surrounding non-coding regions of each gene, followed by bidirectional Sanger sequencing
CaseMethod2: as mentioned
CaseGenotypingMethod: CLN5 genotyping was performed by PCR amplification of the four exons and surrounding non-coding regions was performed, followed by bi-directional Sanger sequencing. Synthetic multiplex ligation-dependent probe amplification (MLPA) was then used to calculate average gene dosage ratio for each ratio, in order to detect large deletions.
Variant: The patient is believed to be homozygous for the NM_006493.4(CLN5):c.936del (p.Phe312LeufsTer4) variant as well as the NM_006493.4(CLN5):c.956A>G (p.Lys319Arg) variant (considered likely benign). The proband is also apparently homozygous for two non-coding variants (an intron 1 variant referred to as "Int1, c.320+8C>T" and a 3'UTR variant referred to as "3'UTR c.1224+33A>G").
ClinVar: 56528 and 128778 (in cis, homozygous)
gnomAD: Maximum allele frequency for the NM_006493.4(CLN5):c.936del (p.Phe312LeufsTer4) variant is 0.0001159 (Latino / Admixed American population, no homozygotes). https://gnomad.broadinstitute.org/variant/13-77574958-AT-A Maximum allele frequency for NM_006493.4(CLN5):c.956A>G (p.Lys319Arg) is 0.4186 (in the African / African-American population, 2136 homozygotes). https://gnomad.broadinstitute.org/variant/13-77574983-A-G
VariantEvidence: NM_006493.4(CLN5):c.936del (p.Phe312LeufsTer4) is a frameshift variant predicted to disrupt ~13% of the protein product. The C-terminal region disrupted has been shown to be glycosylated and is important for proper localization of the protein (PMID:19309691).
CaseAddInfo: Parents are not available for genotyping, so homozygosity of variants is assumed. This conclusion was supported by failure to detect a deletion.
CasePMIDs: N/A
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Mutational screening of splicing factor genes in cases with autosomal dominant retinitis pigmentosa
PMID: 24959063
Gene: PRPF4
HGNC: 17349
Disease: retinitis pigmentosa 70
MONDO: 0014400
InheritancePattern: autosomal dominant
Prevalence: The overall prevalence of retinitis pigmentosa is between 1 in 3,000 and 1 in 4,000 individuals, while the proportion of retinitis pigmentosa with a dominant mode of inheritance is estimated to be 15-35% (between 1 in 8,500 and 1 in 27,000). The proportion of that incidence made up by the specific form caused by variants in PRPF4 is not clear.
Penetrance: Known disease-causing alleles appear to be incompletely penetrant (PMID: 25383878).
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Improving the management of Inherited Retinal Dystrophies by targeted sequencing of a population-specific gene panel
PMID: 27032803
Gene: BBS1
HGNC: 966
Disease: Bardet-Biedl syndrome 1
MONDO: 0008854
InheritancePattern: autosomal recessive
Prevalence: The prevalence of BBS1 variants among Bardet-Biedl syndrome cohorts has been reported as at least 20% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy
PMID: 25766589
Gene: RBP3
HGNC: 9921
Disease: retinitis pigmentosa 66
MONDO: 0014093
InheritancePattern: autosomal recessive
Prevalence: RBP3-related cases are believed to be very rare (possibly with estimated prevalence of less than 1 in 1,000,000), however, it is believed that there may be under-diagnosis (PMID: 37806543).
Penetrance: RBP3 disease-causing variants appear to have complete penetrance.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Using the RPE-specific monoclonal antibody RPE9, raised against human RPE cells, we have identified a novel 65 kD protein, conserved in mammals, birds, and frogs.
Selection A - Gene is expressed in tissues relevant to disease:
ExperimentName: RPE65 expression is highly specific to the retinal pigment epithelium
TissueExpression: pigmented layer of retina (also known as retinal pigment epithelium, UBERON:0001782)
ExpressionEvidence: RPE65 protein was first detected using an RPE-specific monocolonal antibody raised against human retinal pigment epithelium (RPE) cells. Retina-specific gene expression data from a separate publication (PMID: 30239781, https://eyeintegration.nei.nih.gov/) confirm that RPE65 expression is highly specific to the retina relative to other tissues within the eye or the human body in general. Note where the evidence is found in the article.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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Germline Mutations in CTNNB1 Associated With Syndromic FEVR or Norrie Disease
PMID: 30640974
Gene: CTNNB1
HGNC: 2514
Disease: severe intellectual disability-progressive spastic diplegia syndrome
MONDO: 0014035
InheritancePattern: autosomal dominant
Prevalence: The incidence is unknown but estimated to be between 1 in 30,000 and 1 in 40,000 births (PMID: 32168371).
Penetrance: The penetrance of the cognitive impairment phenotype among cases appears to be near-complete, while the exudative vitreoretinopathy phenotype reportedly has a prevalence of ~39% among affected individuals with a syndromic diagnosis.
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www.sciencedirect.com www.sciencedirect.com
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To study the function of GPR143, we investigated the phenotypic effect of overexpression of GPR143 in pheochromocytoma (PC12) cells treated with nerve growth factor. Overexpression of mouse GPR143 inhibited neurite outgrowth, and the effect was mitigated by l-DOPA cyclohexylester, an antagonist for l-DOPA. Furthermore, knockdown of G-protein Gα13 attenuated mouse GPR143 induced inhibition of neurite outgrowth. Human wild-type (wt) GPR143 also inhibited neurite outgrowth, but its mutants did not mimic the effect of wt GPR143. Our results provide a mechanism for axon guidance phenotype in ocular albinism 1.
ExperimentName: GPR143 over-expression in neuroendocrine tumor cells
NonPatientCell: CL:0000336 (adrenal medulla chromaffin cell, specifically the PC-12 cell line)
GeneFunction: GO:0031175 (neuron projection development)
GeneAlteration: Over-expression of GPR143 was accomplished by stable transfection of PC-12 cells with mCherry-tagged wild-type or mutant GPR143.
FunctionalEvidence: Figure 4C indicates that GPR143 over-expression decreases the # of neurites longer than 100 microns, and that this occurs through a mechanism that is dependent on the G-protein Galpha13. Figure 5E shows that this effect of wild-type GPR143 is particularly pronounced for neurites longer than 150 microns, and is not mimicked by GPR143 missense variants reported in patients.
FAVariants: Patient-associated variants were p.Asp78Asn (ClinVar: 98620), p.Trp133Arg (ClinVar: 10516 or 10519), p.Ile261Asn (CAID: CA411996177), and p.Trp292Gly (ClinVar: 98647).
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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c.136C>T (p.Arg46*)
Case#: Khan_2016_Proband_2, male, age 4 months at time of referral, national origin indicated as Saudi
CasePresentingHPOs: Abnormal visual fixation HP:0025404, Nystagmus HP:0000639, Infantile onset HP:0003593, Visual impairment HP:0000505, Deeply set eye HP:0000490, Esotropia HP:0000565, High hypermetropia HP:0008499, Undetectable electroretinogram HP:0000550,
CaseHPOFreeText: The proband has been diagnosed with Leber congenital amaurosis, with poor visual fixation and nystagmus as the presenting features. Staring at lights was a phenotype.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing in the proband consisted of a 44-gene next generation sequencing-based panel for retinal dystrophy showing no other potential cause of retinal features.
CaseMethod1: next-generation sequencing panel (44 genes)
CaseMethod2: Sanger sequencing of PRPH2
CaseGenotypingMethod: Previous testing in the proband consisted of a 44-gene next generation sequencing-based panel for retinal dystrophy showing no other potential cause of retinal features. The presence of the variant was confirmed by Sanger sequencing of PRPH2.
Variant: The proband harbors the NM_000322.5(PRPH2):c.136C>T (p.Arg46Ter) variant in the homozygous state.
ClinVar ID: 13179
gnomAD: The NM_000322.5(PRPH2):c.136C>T (p.Arg46Ter) variant is found in gnomAD v4.0.0 at a frequency of 0.00004005 (3 alleles / 74906 total alleles, with 0 homozygotes) in the African / African-American population https://gnomad.broadinstitute.org/variant/6-42722199-G-A?dataset=gnomad_r4
VariantEvidence: NM_000322.5(PRPH2):c.136C>T (p.Arg46Ter) is a nonsense variant in exon 1 of 3 that is predicted to trigger nonsense-mediated decay or at least to truncate the C-terminal 87% of the protein product.
CaseAddInfo: The proband is the child of first cousin parents who appeared sub-clinically affected but were not genotyped. A second, similarly affected sibling shares the same genotype.
CasePMIDs: N/A
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link.springer.com link.springer.com
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We have studied two Japanese families with SFD, the first report from the Eastern world, and identified a novel 3’ splice site mutation in the TIMP3 gene, namely a single base insertion at the intron 4/exon 5 junction which converts the consensus sequence CAG to CAAG in the splice acceptor site.
GroupName: Tabata_1998_Group
GroupPresentingHPOs: HP:0007663 (Reduced visual acuity), HP:0025094 (Disciform macular scar)
GroupHPOFreeText: Relatively late onset of phenotypes during the 6th, 7th, or 8th decade of life.
GroupNotHPOs: N/A
GroupNotHPOFreeText: N/A
GroupDemographics
NumberMales: 4
NumberFemales: 5
CountryOrigin: Japan
Ethnicity: Not mentioned
Race: Not mentioned
AgeRange: The individuals mentioned range in age from 52 to 75.
TotalNumber: 9
FamilyInfo: 9
NoFamily: 0
VariantCount: 5
NonVariant: 4
OtherVariant: N/A
GroupPreviousTesting: Sanger sequencing of PCR-amplified exon 5
GroupGenotypingMethod: PCR-based heteroduplex analysis using gel electophoresis, as well as SSCP analysis of exon 5.
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis
PMID: 17574030
Gene: BBS7
HGNC: 18758
Disease: Bardet-Biedl syndrome 7
MONDO: 0014435
InheritancePattern: autosomal recessive
Prevalence: The prevalence of BBS7 variants among Bardet-Biedl syndrome cohorts has been reported at 4.2% (PMID: 19402160), while the prevalence of Bardet-Biedl syndrome overall has been estimated between 1 in 13,500 and 1 in 160,000 live births, depending on the population (PMID: 22713813).
Penetrance: The penetrance of the phenotype among homozygous cases appears to be complete.
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www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
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Identification of a novel RPGR mutation associated with X-linked cone-rod dystrophy in a Chinese family
PMID: 34800980
Gene: RPGR
HGNC: 10295
Disease: RPGR-related retinopathy
MONDO: MONDO:0100437
InheritancePattern: X-linked
Prevalence: The prevalence of RPGR-related retinopathy is calculated to be approximately 1 in 214,000, based on the known incidence of retinitis pigmentosa at 1 in 3,000, the proportion of retinitis pigmentposa that is X-linked at 20%, and the proportion of X-linked retinitis pigmentosa that is RPGR-associated at 70% (PMID: 34985506).
Penetrance: Penetrance is nearly 100% in hemizygous males but is incomplete and dependent upon the variant in heterozygous female carriers.
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