The consequences of telomerase deficiency were studied in model organisms before telomerase mutations were discovered in the setting of human disease[18, 19]
Animal Models telomerase deficiency was studied in mouse models prior to their discovery in association with human disease, with dyskeratosis congenita being the first to be associated with TBD
The consequences of telomerase deficiency were studied in model organisms before telomerase mutations were discovered in the setting of human disease[18, 19]
Animal Models telomerase deficiency was studied in mouse models prior to their discovery in association with human disease, with dyskeratosis congenita being the first to be associated with TBD
Clinical and genetic characteristics of concomitant Mucopolysaccharidosis type IVA and neurogenic bladder in children: two case reports and literature review
PMID 33407246
Disease Mucopolysaccharidosis IVA
Gene GALNS
Clinical and genetic characteristics of concomitant Mucopolysaccharidosis type IVA and neurogenic bladder in children: two case reports and literature review
PMID 33407246
Disease Mucopolysaccharidosis IVA
Gene GALNS
Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia
PMID: 26769677
Gene: ELP1
Disease: Familial dysautonomia
MonDO: MONDO:0009131
InheritancePattern: AR
Notes: Morini_Mouse
Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia
PMID: 26769677
Gene: ELP1
Disease: Familial dysautonomia
MonDO: MONDO:0009131
InheritancePattern: AR
Notes: Morini_Mouse
Mucopolysaccharidosis IVA: Identification of a Common Missense Mutation I113F in the N-Acetylgalactosamine-6-Sulfate Sulfatase Gene
PMID: 7668283
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
Mucopolysaccharidosis IVA: Identification of a Common Missense Mutation I113F in the N-Acetylgalactosamine-6-Sulfate Sulfatase Gene
PMID: 7668283
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
RESULTS
NonHumanModel: Murine
GeneAlteration: murine Galns portions of intron 1 and exon 2 were deleted via homologous recombination of a cre-neomycin resistance-cre cassette and mated with a cre recombinase strain to remove the cassette and complete the deletion
ModelPhenotype: No outward phenotypes but biochemically there was up to a 6 fold increase in GAG excretion in urine, chondroitin-6-sulfate specifically and not keratan sulfate, consistent with the human phenotype
HumanPhenotype: in severe cases there are obvious skeletal deformations, increase of GAG's chondroitin-6-sulfate and keratan sulfate in urine and decreased or absent GALNS activity
ModelEvidence: X-rays of mice and multiple life stages, GAG assays in urine, immunohistochemistry images of tissues with labeled chondoritin-6-sulfate and keratan sulfate to show distribution in multiple tissue types and
ModelVariant: large deletion of portion of intron 1 and exon 2
WhereInPaper:
RESULTS
NonHumanModel: Murine
GeneAlteration: murine Galns portions of intron 1 and exon 2 were deleted via homologous recombination of a cre-neomycin resistance-cre cassette and mated with a cre recombinase strain to remove the cassette and complete the deletion
ModelPhenotype: No outward phenotypes but biochemically there was up to a 6 fold increase in GAG excretion in urine, chondroitin-6-sulfate specifically and not keratan sulfate, consistent with the human phenotype
HumanPhenotype: in severe cases there are obvious skeletal deformations, increase of GAG's chondroitin-6-sulfate and keratan sulfate in urine and decreased or absent GALNS activity
ModelEvidence: X-rays of mice and multiple life stages, GAG assays in urine, immunohistochemistry images of tissues with labeled chondoritin-6-sulfate and keratan sulfate to show distribution in multiple tissue types and
ModelVariant: large deletion of portion of intron 1 and exon 2
WhereInPaper:
Genetics of human telomere biology disorders
PMID 36151328
Gene TERC
Diseases dyskeratosis congenita, pulmonary fibrosis, Høyeraal–Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome
This is substantiated by the observation that, similarly to some types of SGR that affect the RNA decay machinery (for example, DIS3 or MTREX; Fig. 4c) and likely increase the level of functional hTR, an inhibitor of the hTR poly(A) polymerase PAPD5 increases the level of mature hTR and improves the potential of haematopoietic stem and progenitor cells in the context of PARN or dyskerin deficiency59,237,238,239.
potential gene therapy targets to increase TERC (hTR)
Since then, 16 additional TBD-causing genes have been identified (Table 1)
Important Table of 16 known telomere biology disorder linked genes with synopses of associated diseases and case counts
Genetics of human telomere biology disorders
PMID 36151328
Gene TERC
Diseases dyskeratosis congenita, pulmonary fibrosis, Høyeraal–Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome
This is substantiated by the observation that, similarly to some types of SGR that affect the RNA decay machinery (for example, DIS3 or MTREX; Fig. 4c) and likely increase the level of functional hTR, an inhibitor of the hTR poly(A) polymerase PAPD5 increases the level of mature hTR and improves the potential of haematopoietic stem and progenitor cells in the context of PARN or dyskerin deficiency59,237,238,239.
potential gene therapy targets to increase TERC (hTR)
Since then, 16 additional TBD-causing genes have been identified (Table 1)
Important Table of 16 known telomere biology disorder linked genes with synopses of associated diseases and case counts
Short telomeres are a risk factor for idiopathic pulmonary fibrosis
PMID 18753630
Disease pulmonary fibrosis
Short telomeres are a risk factor for idiopathic pulmonary fibrosis
PMID 18753630
Disease pulmonary fibrosis
Mucopolysaccharidosis IVA and glycosaminoglycans
PMID: 27979613
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Review
Glycosaminoglycans: KS and C6S
ExperimentName: Accumulation of glycosaminoglycans
GOterm:
FunctionalEvidence: Patient cells assayed with artificial substrates for the N-acetylgalactosamine-6-sulfate sulfatase encoded by GALNS, depending on the severity of the coding sequence alteration, are either unable to break down the substrate or are hindered. Further, in mucopolysaccharidosis IVA patients with known variants, elevated levels of keratan sulfate and chondroitin-6-sulfate can be found in their urine where levels in unaffected individuals are much lower.
HGNC:
GeneEvidence:
SharedGeneImplication:
Mucopolysaccharidosis IVA and glycosaminoglycans
PMID: 27979613
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Review
Glycosaminoglycans: KS and C6S
ExperimentName: Accumulation of glycosaminoglycans
GOterm:
FunctionalEvidence: Patient cells assayed with artificial substrates for the N-acetylgalactosamine-6-sulfate sulfatase encoded by GALNS, depending on the severity of the coding sequence alteration, are either unable to break down the substrate or are hindered. Further, in mucopolysaccharidosis IVA patients with known variants, elevated levels of keratan sulfate and chondroitin-6-sulfate can be found in their urine where levels in unaffected individuals are much lower.
HGNC:
GeneEvidence:
SharedGeneImplication:
Molecular analysis of the PAX6 gene in Mexican patients with congenital aniridia: report of four novel mutations
PMID: 18776953
Gene: PAX6
Variant c.-129+9G>A
Disease: Ocular dysgenesis
MonDO: MONDO:0700246
InheritancePattern: AD
Molecular analysis of the PAX6 gene in Mexican patients with congenital aniridia: report of four novel mutations
PMID: 18776953
Gene: PAX6
Variant c.-129+9G>A
Disease: Ocular dysgenesis
MonDO: MONDO:0700246
InheritancePattern: AD
A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient
PMID: 19607881
Variant NM_001368894.2:c.136C>G(p.Leu46Val)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
A novel missense mutation (Leu46Val) of PAX6 found in an autistic patient
PMID: 19607881
Variant NM_001368894.2:c.136C>G(p.Leu46Val)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
A novel deletion (IVS11+3del4) identified in the human PAX6 gene in a patient with aniridia
PMID:
Gene: PAX6
Variant NM_000280.5:c.333C>A(p.Val111=)
Disease: Ocular dysgenesis
InheritancePattern: AD
Notes In Table 1. and Figure 3 there are nice illustrations of the consequences of this variant leading to a 27bp truncation in exon 6, in frame, which causes an AA deletion p.Cys112_Val120del version of PAX6. No patient phenotype data is available.
A novel deletion (IVS11+3del4) identified in the human PAX6 gene in a patient with aniridia
PMID:
Gene: PAX6
Variant NM_000280.5:c.333C>A(p.Val111=)
Disease: Ocular dysgenesis
InheritancePattern: AD
Notes In Table 1. and Figure 3 there are nice illustrations of the consequences of this variant leading to a 27bp truncation in exon 6, in frame, which causes an AA deletion p.Cys112_Val120del version of PAX6. No patient phenotype data is available.
Four patients (2 males, 2 females)
Case#: Fateen_P4
Demographics: Egyptian
CasePresentingHPOs: HP:0000768, HP:0000943, HP:0002857, HP:0000256, HP:0002808, HP:0001382, HP:0005072, HP:0009769 prominent proximal metaphyses
CaseNotHPOs:
CasePreviousTesting:
CaseMethod1:
CaseMethod2:
CaseGenotypingMethod: single gene seq by Sanger of all 14 exons and restriction digest confirmation/ screening of parents and controls
Variant: NM_000512.5(GALNS):c.119A>G (p.Asp40Gly)
ClinVar: 1048369
CAID: CA397100962
gnomAD: n/a
VariantEvidence: hydrophillic>hydrophobic substitution in putative active site and enzyme activity data shows low enzyme function compared to reference range
CaseAddInfo:
CasePMIDs:
Four patients (2 males, 2 females)
Case#: Fateen_P4
Demographics: Egyptian
CasePresentingHPOs: HP:0000768, HP:0000943, HP:0002857, HP:0000256, HP:0002808, HP:0001382, HP:0005072, HP:0009769 prominent proximal metaphyses
CaseNotHPOs:
CasePreviousTesting:
CaseMethod1:
CaseMethod2:
CaseGenotypingMethod: single gene seq by Sanger of all 14 exons and restriction digest confirmation/ screening of parents and controls
Variant: NM_000512.5(GALNS):c.119A>G (p.Asp40Gly)
ClinVar: 1048369
CAID: CA397100962
gnomAD: n/a
VariantEvidence: hydrophillic>hydrophobic substitution in putative active site and enzyme activity data shows low enzyme function compared to reference range
CaseAddInfo:
CasePMIDs:
phenotype of the Australian kindred is similar to the basal ganglia disorder (Waisman syndrome [MIM 311510]) reported for a Wisconsin kindred5 (Figure 1; Table S1). Members of the defining family included 13 affected males who presented with variable degrees of ID and early-onset parkinsonism. Multipoint linkage analysis of the Wisconsin family previously localized the disease-causing mutation to Xq27.3–qter with a maximum multipoint LOD of 6.75 at the genetic marker F8C (chrX:154,929,351–154,929,630; GRCh38/hg38).
Wilson_Wisconsin kindred
Family#PresentingHPOs: HP:0001263, HP:0000750, HP:0001249, HP:0002174, HP:0007351, HP:0002362, HP:0002067, HP:0002396, HP:0001260, HP:0000256, HP:0002007, HP:0000218, HP:0001355,
Age at clinical evaluation <2y; early learning difficulty with ability to read and live independently (in some members), age at tremor onset 10-20y, age at Parkinson diagnosis 20s, absent response to L-Dopa, hypokinetic dysarthria, skin depigmented papules, normal cerebellar function and eye examination, normal karyotype, normal copper testing, normal blood count and chemistry, normal urine metabolic testing, normal hearing.
FamilyNotHPOs:
Fragile X syndrome,
CountryOrigin: Germany
Ethnicity:
Race:
Family#PreviousTesting: Multipoint linkage analysis was performed. X chromosome exome sequencing revealed no other variants in the linkage region. Direct sequencing of CLIC2 ruled out variants in the gene.
Family#Method1: Sanger seq
Family#Method2:
Family#GenotypingMethod: RAB39B was directly sequenced
Affected: 16
Unaffected:
Segregations:
PublishedLOD: 6.75
eLOD:
AddSegregationInfo:
ProbandLabel: Wilson_Wisconsin kindred proband
Variant: NM_171998.4(RAB39B):c.503C>A (p.Thr168Lys)
ClinVar: 156532
CAID:
gnomAD: NR
FamilyAddInfo: Family is noted to be of German ancestry, and no consanguinity is noted.
FamilyPMIDs: 1674730, 4025396
We identified an Australian kindred with three brothers who presented in childhood with nonprogressive intellectual disability (ID), which included delayed developmental milestones, cognitive impairment, and macrocephaly
Case#: Wilson_Australian kindred_Person II:2
Demographics: Male, 44y at diagnosis, Australia
CasePresentingHPOs: HP:0000750, HP:0001249, HP:0007351, HP:0002362, HP:0002067, HP:0100660, HP:0002396, HP:0000256
Age at onset <2y, while age at tremor onset was 38y. Birth and early milestones were normal. Early learning difficulties were reported and the proband was able to read and write. Parkinsonism classification was akinetic-rigid. Proband showed L-Dopa response, hypokinetic dysarthria, and normal cerebellar function. Other normal features included normal eye examination, MRI, Fragile X testing, karyotype, Copper testing, blood count and chemistry, urine metabolic testing and hearing.
CaseNotHPOs:
CasePreviousTesting: Linkage analysis using homozygous recessive model identified no linkage to autosomes, but to two regions: Xp22.2 and Xq27.3–qter
CaseMethod1: Copy number variation analysis
CaseMethod2: PCR
CaseGenotypingMethod: A ~45-kb deletion within the Xq haplotype was identified that encompassed the complete RAB39B gene and the last 3 coding exons of CLIC2.
Variant: NC_000023.11:g.(155246216_?)_(?_155288781)del
ClinVar: 157665
CAID:
gnomAD:
VariantEvidence: The proband was hemizygous for the ~45-kb deletion encompassing the complete RAB39B and partial CLIC2 genes. Expression of both transcripts was absent from fibroblast cells of affected individuals. The proband is not scored any points as the variant involves deletion of part of an additional gene, CLIC2. Although the authors ruled out seizures and cardiac anomalies (phenotypes associated with CLIC2 missense variant) in patients from the family, it is not conclusive that CLIC2 deletion does not have any impact on the proband's phenotype.
CaseAddInfo: The proband's siblings were also similarly affected. Elder brother of the proband died at 48y from positional asphyxia, and postmortem neuropathological studies on proband's brain showed pallor of the substantia nigra and locus coeruleus. H&E staining of substantia nigra revealed PD features, including loss of pigmented neurons and Lewy bodies in surviving neurons. Abundance of cortical Lewy bodies, were noted. Tau-immunoreactive NFTs were also observed in a small proportion of the surviving pigmented SN neurons
CasePMIDs:
phenotype of the Australian kindred is similar to the basal ganglia disorder (Waisman syndrome [MIM 311510]) reported for a Wisconsin kindred5 (Figure 1; Table S1). Members of the defining family included 13 affected males who presented with variable degrees of ID and early-onset parkinsonism. Multipoint linkage analysis of the Wisconsin family previously localized the disease-causing mutation to Xq27.3–qter with a maximum multipoint LOD of 6.75 at the genetic marker F8C (chrX:154,929,351–154,929,630; GRCh38/hg38).
Wilson_Wisconsin kindred
Family#PresentingHPOs: HP:0001263, HP:0000750, HP:0001249, HP:0002174, HP:0007351, HP:0002362, HP:0002067, HP:0002396, HP:0001260, HP:0000256, HP:0002007, HP:0000218, HP:0001355,
Age at clinical evaluation <2y; early learning difficulty with ability to read and live independently (in some members), age at tremor onset 10-20y, age at Parkinson diagnosis 20s, absent response to L-Dopa, hypokinetic dysarthria, skin depigmented papules, normal cerebellar function and eye examination, normal karyotype, normal copper testing, normal blood count and chemistry, normal urine metabolic testing, normal hearing.
FamilyNotHPOs:
Fragile X syndrome,
CountryOrigin: Germany
Ethnicity:
Race:
Family#PreviousTesting: Multipoint linkage analysis was performed. X chromosome exome sequencing revealed no other variants in the linkage region. Direct sequencing of CLIC2 ruled out variants in the gene.
Family#Method1: Sanger seq
Family#Method2:
Family#GenotypingMethod: RAB39B was directly sequenced
Affected: 16
Unaffected:
Segregations:
PublishedLOD: 6.75
eLOD:
AddSegregationInfo:
ProbandLabel: Wilson_Wisconsin kindred proband
Variant: NM_171998.4(RAB39B):c.503C>A (p.Thr168Lys)
ClinVar: 156532
CAID:
gnomAD: NR
FamilyAddInfo: Family is noted to be of German ancestry, and no consanguinity is noted.
FamilyPMIDs: 1674730, 4025396
Exome Sequencing Identifies a Biallelic GALNS Variant (p.Asp233Asn) Causing Mucopolysaccharidosis Type IVA in a Pakistani Consanguineous Family
PMID: 36292628
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Case report
Exome Sequencing Identifies a Biallelic GALNS Variant (p.Asp233Asn) Causing Mucopolysaccharidosis Type IVA in a Pakistani Consanguineous Family
PMID: 36292628
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes: Case report
The clinical and functional effects of TERT variants in myelodysplastic syndrome
PMID 34019641
Phenotypes HP:0031413, HP:0002863
Phenotypes free-text short telomere length, myelodysplastic syndrome
The clinical and functional effects of TERT variants in myelodysplastic syndrome
PMID 34019641
Phenotypes HP:0031413, HP:0002863
Phenotypes free-text short telomere length, myelodysplastic syndrome
Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism
PMID 30098700
Mutation profiles and clinical characteristics of Chinese males with isolated hypogonadotropic hypogonadism
PMID 30098700
PMID: 9536098
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
PMID: 9536098
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
Lost in translation: returning germline genetic results in genome-scale cancer research
PMID: 28454591
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Lost in translation: returning germline genetic results in genome-scale cancer research
PMID: 28454591
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations and genotype–phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea J.H. Kim, J.H. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorM.-W. Seong, M.-W. Seong Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorK.E. Lee, K.E. Lee Department of Surgery, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorH.J. Choi, H.J. Choi Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South KoreaSearch for more papers by this authorE.J. Ku, E.J. Ku Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorJ.H. Bae, J.H. Bae Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.S. Park, S.S. Park Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.H. Choi, S.H. Choi Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.W. Kim, S.W. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorCS Shin, CS Shin Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.Y. Kim, Corresponding Author S.Y. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South Korea Corresponding author: Prof Seong Yeon Kim, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 110-744, South Korea. Tel.: 082-02-2072-3216; fax: 082-02-762-9662; e-mail: seongyk@plaza.snu.ac.krSearch for more papers by this author
PMID: 24134185
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations and genotype–phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea J.H. Kim, J.H. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorM.-W. Seong, M.-W. Seong Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaBoth the authors contributed equally to this work.Search for more papers by this authorK.E. Lee, K.E. Lee Department of Surgery, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorH.J. Choi, H.J. Choi Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, South KoreaSearch for more papers by this authorE.J. Ku, E.J. Ku Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorJ.H. Bae, J.H. Bae Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.S. Park, S.S. Park Department of Laboratory medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.H. Choi, S.H. Choi Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.W. Kim, S.W. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorCS Shin, CS Shin Department of Internal medicine, Seoul National University College of Medicine, Seoul, South KoreaSearch for more papers by this authorS.Y. Kim, Corresponding Author S.Y. Kim Department of Internal medicine, Seoul National University College of Medicine, Seoul, South Korea Corresponding author: Prof Seong Yeon Kim, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 110-744, South Korea. Tel.: 082-02-2072-3216; fax: 082-02-762-9662; e-mail: seongyk@plaza.snu.ac.krSearch for more papers by this author
PMID: 24134185
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Sequence Variations in the von Hippel–Lindau Tumor Suppressor Gene in Patients with Intracranial Aneurysms
PMID: 23434161
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Sequence Variations in the von Hippel–Lindau Tumor Suppressor Gene in Patients with Intracranial Aneurysms
PMID: 23434161
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Outcome and genetic analysis of patients affected by retinal capillary hemangioblastoma in von Hippel Lindau syndrome
PMID: 34566400
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Outcome and genetic analysis of patients affected by retinal capillary hemangioblastoma in von Hippel Lindau syndrome
PMID: 34566400
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan
PMID: 8956040
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Germline mutations in the Von Hippel-Lindau disease (VHL) gene in families from North America, Europe, and Japan
PMID: 8956040
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
A case of 3p deletion syndrome associated with cerebellar hemangioblastoma
PMID: 26365017
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
A case of 3p deletion syndrome associated with cerebellar hemangioblastoma
PMID: 26365017
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Associations between VHL genotype and clinical phenotype in familial von Hippel-Lindau disease
PMID: 17537157
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Associations between VHL genotype and clinical phenotype in familial von Hippel-Lindau disease
PMID: 17537157
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease
PMID: 19649731
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation screening of VHL gene in a family with malignant bilateral pheochromocytoma: from isolated familial pheochromocytoma to von Hippel-Lindau disease
PMID: 19649731
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Pheo-Type: A Diagnostic Gene-expression Assay for the Classification of Pheochromocytoma and Paraganglioma
PMID: 26796762
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Pheo-Type: A Diagnostic Gene-expression Assay for the Classification of Pheochromocytoma and Paraganglioma
PMID: 26796762
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Von Hippel Lindau Disease
PMID: 30853203
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Von Hippel Lindau Disease
PMID: 30853203
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Clear cell chondrosarcoma in Von Hippel-Lindau disease
PMID: 31673890
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Clear cell chondrosarcoma in Von Hippel-Lindau disease
PMID: 31673890
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas
PMID: 16142346
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Three novel VHL germline mutations in Korean patients with von Hippel-Lindau disease and pheochromocytomas
PMID: 16142346
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene
PMID: 8550742
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Familial pheochromocytoma associated with a novel mutation in the von Hippel-Lindau gene
PMID: 8550742
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation of the Von Hippel-Lindau tumour suppressor gene in capillary haemangioblastomas of the central nervous system
PMID: 8758206
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Mutation of the Von Hippel-Lindau tumour suppressor gene in capillary haemangioblastomas of the central nervous system
PMID: 8758206
Gene: VHL
StandardizedReferenceSequence: NM_000551.3
Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia
PMID: 18241071
Gene: PAX6
Variant NM_001368894.2:c.-128-2del
Disease: Ocular dysgenesis
InheritancePattern: AD
Disease PAX6-related ocular dysgenesis MONDO:0800183
X-linked Parkinsonism with Intellectual Disability caused by novelmutations and somatic mosaicism inRAB39Bgene
PMID: 28851564
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
Extension of the mutation spectrum of PAX6 from three Chinese congenital aniridia families and identification of male gonadal mosaicism
PMID: 30334364
Variant NM_000280.5:c.1123C>A (p.Pro375Thr)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
Hexb enzyme deficiency leads to lysosomal abnormalities in radial glia and microglia in zebrafish brain development
PMID: 31140649
Gene: HEXB
Disease: Sandhoff Disease
MonDO: MONDO:0010006
Loss of human ICOSL results in combined immunodeficiency
PMID: 30498080
Gene: ICOSLG
Disease: Combined Immunodeficiency
MonDO: MONDO:0015131
InheritancePattern: Autosomal recessive pattern
Shi, 2016 - A novel RAB39B gene mutation in X-linked juvenile parkinsonism with basal ganglia calcification
PMID: 27943471
Gene: RAB39B
Disease: early-onset parkinsonism-intellectual disability syndrome
MonDO: MONDO:0010709
A new PAX6 mutation in familial aniridia
PMID: 7666404
Variant NM_001368894.2:c.1225G>C(p.Gly409Arg)
Gene: PAX6
Disease: Ocular dysgenesis
InheritancePattern: AD
Notes SNP at last nucleotide in exon 13 leads to loss of donor site and exon skipping event.
Peptide neurotransmitters activate a cation channel complex of NALCN and UNC-80
PMID 19092807 Gene: UNC80
RNA analysis of the GALNS transcript reveals novel pathogenic mechanisms associated with Morquio syndrome A
PMID: 35782621
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
Notes:
Mucopolysaccharidosis type IVA. N-acetylgalactosamine-6-sulfate sulfatase exonic point mutations in classical Morquio and mild cases.
PMID: 1522213
Gene: GALNS
Disease: Mucopolysaccharidosis IVA
MonDO: MONDO:0009659
InheritancePattern: AR
ExperimentName: Expression of variant carrying cDNA in GALNS deficient fibroblasts
FunctionalEvidence: cDNA encoding each of the 15 variants identified in the study were transfected into a GALNS deficient fibroblast cell line. 14 of the 15 altered cDNA's showed no increase in GALNS activity when the cells were assayed, confirming a lack of enzymatic activity.
HGNC:
GeneEvidence:
SharedGeneImplication:
The proband of thisfamily (Patient #4
Case#: Male, Family #2, patient #4, onset at 48y.o
DiseaseAssertion: STGD
FamilyInfo: proband sister(#3) identical ABCA4 allele to proband, developed central vision issues. Proband son has complex allele w/ early onset cone-rod dystrophy. Proband daughter(#6) has complex allele mutation, central vision issues developed at 17. retinal exam showed atrophic macular lesions. Proband second daughter(patient #5, asymptomatic)
CasePresentingHPOs: HP:0012508, HP:0030500
CaseHPOFreeText:Proband presented with bull's eye macular lesions with no fundus flecks. Normal rod-mediated amplitudes, normal single-flash response, reduces 32-Hz flicker amplitude.
CaseNotHPOs: n/a
CaseNotHPOFreeText: maintained foveal sparing in both eyes 20/25+2 R.E, 20/25+1 L.E.
Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.
PreviouslyPublished: n/a
Variant: c.4139C>T (p.P1380L), BoldM1: c.5603A>T(p.N18681)[NM_000350.3(ABCA4):c.5603A>T (p.Asn1868Ile) - Variation ID 99390], M2: c.[1622T>C; 3113C>T] (p.[L541P; A1308V])
ClinVar: M1) 99390 M2) 99067
CAID: n/a
SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom
The proband of Family #4
Case#: Female, Family #4, patient #8
DiseaseAssertion: STGD
FamilyInfo: Proband's daughter shares ABCA4 variant and struggled with difficulty focusing at age 19. BVCA 20/200 R.E and 20/80 in L.E.
CasePresentingHPOs: HP:0030500, HP:0007663, HP:0000608
CaseHPOFreeText: Proband's first symptom was difficulty with night vision occurring at 45 y.o, BVCA at 50 y.o in both eyes was 20/20. atrophy in macula and Stage 2 fundus flecks identified.
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.
PreviouslyPublished: n/a
Variant: NM_000350.3(ABCA4):c.1622T>C (p.Leu541Pro), NM_000350.3(ABCA4):c.1957C>T (p.Arg653Cys)
ClinVar: M2) 99067, M5) 99108
CAID: n/a
SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom
son (the proband of Family #3, pedigree in Figure 1C)
Case#: Male, Family#3, Proband M1, M2: II,1 on pedigree
DiseaseAssertion: STGD
FamilyInfo: mother of proband has p.N18681 and p.P1380L mutations and is asymptomatic with no changes to NIR-AF and SD-OCT. Treated with 400mg of hydroxychloroquine for lupus prior to imaging. Non-affected father.
CasePresentingHPOs:HP:0007663, HP:0000493
CaseHPOFreeText: Proband has reduced visual acuity and issues reading with BCVA 20/200 in R.E and 20/50-2 in L.E. Oval foveal lesions with stage 2 flecks. Visual acuity reducing starting at age 10.
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.
PreviouslyPublished: n/a
Variant: M1:p.P1380L, complex allele: M2: p.N18681 and IVS38:c.5461-10T>C. M3: c.4139C>T(p.P1380L)
ClinVar: M1) 99390 M2) 99067 M3) Variation ID: 7904
CAID: n/a
SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom
The proband (Patient #20
Case#: Female, family #5, Patient #20
DiseaseAssertion: STGD
FamilyInfo: Proband's sister presented with same clinical prognosis. Sister diagnosed with pattern dystrophy and photoaversion at age 57, with difficulty seeing at night. Sister has nuclear sclerotic and cortical cataracts in both eyes.
CasePresentingHPOs: HP:0000662, HP:0000603, HP:0000603, HP:0000493
CaseHPOFreeText: Proband presented with localized blur at age 62, (late onset) in her left eye. BVCA 20/20-3 and 20/20-2 at age 70. Also has macular lesions with stage 2 fundus flecks.
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.
PreviouslyPublished: n/a
Variant: p.N18681, IVS36:c.5196+1G>A
ClinVar: M2) 99067, M6) 99351
CAID: N/A
SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom
proband
Case#: Two affected sisters/Female siblings/Progressive onset initially presenting as Stargardt disease
DiseaseAssertion: ABCA4
FamilyInfo: Large American family pedigree with two affected sisters. Both sisters were compound heterozygous for two novel ABCA4 variants. Unaffected relatives carried one variant or neither variant, supporting autosomal recessive inheritance.
CasePresentingHPOs: HP:0000556, HP:0000572, HP:0007754, HP:0000648, HP:0000510, HP:0001133, HP:0000610
CaseHPOFreeText: Proband initially showed phenotype compatible with Stargardt disease with progressive central vision loss. Over several years disease advanced into severe cone-rod dystrophy with worsening retinal degeneration, abnormal visual fields, and reduced electroretinography responses.
CaseNotHPOs: n/a
CaseNotHPOFreeText: Unaffected family members with only one mutation had no retinal disease phenotype.
Genotyping Method: Genome-wide linkage analysis using 408 microsatellite markers followed by direct Sanger DNA sequencing of all ABCA4 exons and exon-intron boundaries. Segregation analysis performed in family members.
PreviouslyPublished: No, both variants were novel at time of publication.
Variant: ABCA4 (RefSeq: NM_000350.3): c.655A>T ; ABCA4 (RefSeq: NM_000350.3): c.5312+3A>T
ClinVar: 632118
CAID: n/a
SupplementalData: Variants absent in 200 unrelated controls. Clinical testing included visual acuity, fundus examination, fluorescein angiography, visual field testing, and electroretinography. Compound heterozygous state associated with severe progressive phenotype.
54-year-old female patient
Case#: Female, 54 yo
FamilyInfo: No family members were available
CasePresentingHPOs: HP:0007924, HP:0000519,HP:0001105, HP:0030825,
CaseHPOFreeText: diagnosed with HIV 15 years ago. She was initially diagnosed with HIV following recurrent respiratory infections and an unintentional weight loss of 12 kg over six months. The diagnosis was confirmed via a positive HIV antibody test, followed by a Western blot confirmation and a CD4 count of 400 cells/mm³ at the time of diagnosis. Antiretroviral therapy (ART) was initiated shortly after confirmation of the diagnosis. Her condition has since progressed to AIDS, with a recent CD4 count of 80 cells/mm³. She was on ART, including tenofovir, emtricitabine, and efavirenz.
CaseNotHPOs: n/a
GenotypeMethod: NGS, Sanger Sequencing
Variant: c.2588G>C in exon 13, c.5461-10T>C in intron 39
ClinVar: Not reported in ClinVar
**SupplementalData: ** indicative of significant loss of central retinal structure (Figure 4).
Intersection of Stargardt Dystrophy and AIDS: A Case Report
PMID:39991341
Gene: ABCA4
Disease: Stargardt
ABCA4-related retinopathies in Lebanon
PMID: 38694055 Gene: ABCA4
Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters
Age of onset
Case #: Eldest sister/Female/Onset at 3yo
DiseaseAssertion: SLC26A2
FamilyInfo: Family pedigree showing consanguinity of the proband's parents. The osteochondrodysplasia genotype, derived from a homozygous variant in the SLC26A2 gene and compound heterozygous variants in the ABCA4 gene, is responsible for the retinal phenotype
CasePresentingHPOs: HP:0034345, HP:0000556, HP:0002098, HP:0001903, HP:0001385, HP:0007754, HP:0002650, HP:0000939, HP:0025388, HP:0007987, HP:0003124, HP:0007401
CaseHPOFreeText: Visual acuity was 1/50 and 2/50 for both eyes, knee dysplasia, sticky platelet syndrome type II
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
GenotypyingMethod: genetic screening by next‐generation sequencing (NGS) was performed on a panel of genes involved in retinal dystrophy and macular degeneration
PreviouslyPublished: n/a
Variant: ABCA4 (RefSeq: NM_000350.3(ABCA4):c.203C>T (p.Pro68Leu))
CAID: n/a
SupplementalData: Comparison of phenotypes (table 1)
231
Case#: Patient 231, Female, age of onset at 7 y.o, Poland
DiseaseAssertion: STGD1
FamilyInfo: Mother was a carrier, unaffected father.
CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158
CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.
Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.
PreviouslyPublished: yes
Variant: c.4234C>T , p.(Gln1412*)
ClinVar: 99263
gnomeAD 0.00001984 allelic frequency
CAID: n/a
SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.
c.634C>T
Case#: Patient 225, Female, age of onset 7 y.o, Poland
DiseaseAssertion: STGD-1
FamilyInfo: no given family information.
CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158
CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.
Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.
PreviouslyPublished: yes
Variant: c.634C>T,p.(Arg212Cys)
ClinVar: 7898
CAID: n/a
gnomeAD 0.0001177 allele frequency
SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.
c.5882G>A
Case#: Patient 231, Female, age of onset at 7 y.o, Poland
DiseaseAssertion: STGD1
FamilyInfo: Mother was a carrier, unaffected father.
CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158
CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.
Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.
PreviouslyPublished: yes
Variant: c.5882G>A
ClinVar:7888
gnomeAD: 0.00310 allelic freq.
CAID: n/a
SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.
F17-003
Case#: Patient 225, Female, age of onset 7 y.o, Poland
DiseaseAssertion: STGD-1
FamilyInfo: no given family information.
CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158
CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.
Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.
PreviouslyPublished: yes
Variant: c.[1622T>C;3113C>T]
ClinVar: 99067, 7894
CAID: n/a
gnomeAD 0.0001266 allele frequency
SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.
Late-onset Stargardt disease
PMID: 35243166
Gene: ABCA4
HGNC: 34
Novel ABCA4 compound heterozygous mutations cause severe progressive autosomal recessive cone-rod dystrophy presenting as Stargardt disease
PMID: 19352439
Gene: ABCA4
Novel compound heterozygous mutations in ABCA4 in a Chinese pedigree with Stargardt disease
PMID: 28050124 Gene: ABCA4 HGNC: HGCN:34
Patient 1
Case#: Patient 1, Female, age 40
DiseaseAssertion: STGD1
FamilyInfo: n/a
CasePresentingHPOs: HP:0007722, HP:0000608, HP:0000007
CaseHPOFreeText: Patient diagnosed with STGD type 1, presenting with retinal pigment atrophy as well as other symptoms typical of STGD1 with reduced visual acuity. Patient daignosed at age 16.
CaseNotHPOs: n/a
CaseNotHPOFreeText: n/a
Genotyping Method: Patient ABCA-4 gene sequenced via Sanger sequencing of all 50 exons, Splice variants were identified by synthesized cDNA from RNA isolation with RT-PCR analysis with exonic primers.
PreviouslyPublished: Variant 1 identified in association with retinal dystrophy in these PMC articles: 23982839, 25082829, 25082885, 28327576
Variant: NM_000350.3(ABCA4):c.859-9T>C, NM_000350.3(ABCA4):c.303-3C>G
ClinVar: 3249248, 859348
gnomAD total allele frequency: 0.005% of var . 1
CAID: n/a
SupplementalData: Fig 1: Minigene RNA analysis of splice variants. A: genomic region of exon 40 on ABCA-4. B: genomic regions of exons 39-41 to investigate specific variant:oncanonical splice site variant c.5714+5G>A Fig 2: overview of wild-type midigene splice constructs of ABCA-4 and locations of 47 different non canonical splice site variants Fig 3: Overview of splice defects from nine different non canonnical splice variants in ABCA-4 gene. Fig 4: percentages of normal ABCA-4 transcripts as a result of noncanonical splice variants using electrophoresis system analysis. Table 1: Non canonical splice variants and observed protein affects.
35-year-old woman
**Case#: ** Female, 35yo
FamilyInfo: Unremarkable
CasePresentingHPOs: HP:0000529 Progressive visual loss, HP:0030532 Visual acuity, HP:0007401 Macular atrophy
CaseHPOFreeText: 35-year-old woman presented with symptom of gradually progressive diminution of vision in both eyes since childhood. Patient gave no history of defective night vision.
CaseNotHPO n/a
GenoTypeMethod: n/a (optical coherence tomography (OCT))
Antisense oligonucleotide therapy corrects splicing in the common Stargardt disease type 1-causing variant ABCA4 c.5461-10T>C
PMID:36910710 Gene: ABCA4 HGNC: 34
Patient 2, a 46-year-old Caucasian woman, presented in July 1998 with a history of progressive decline in visual acuity since the age of 16
PMID: 10612508
Gene: ABCA4
Case#: Patient 2, 46-year-old female
DiseaseAssertion: STGD1
FamilyInfo: One of four affected siblings in a family consistent with autosomal recessive inheritance.
CasePresentingHPOs: HP:0000545 — Decreased visual acuity HP:0007754 — Macular atrophy HP:0030638 — Retinal flecks HP:0000512 — Abnormal fundus morphology
CaseHPOFreeText: Progressive visual decline since age 16. Best-corrected visual acuity 20/400 in both eyes. Fundus examination showed bilateral symmetrical central chorioretinal atrophy (~3 disc diameters) with prominent pigment deposits and numerous yellow flecks in the posterior pole. Fluorescein angiography demonstrated central hypofluorescence with surrounding hyperfluorescence and peripheral dark choroid.
CaseNotHPOs: Not reported
CaseNotHPOFreeText: Not reported
GenotypingMethod: PCR amplification and direct sequencing of ABCA4 after SSCP screening
PreviouslyPublished: Yes
Variant: NM_000350.2:c.2588G>C (p.Gly863Ala) NM_000350.2:c.161G>A (p.Cys54Tyr)
ClinVar: Not reported
CAID: Not reported
SupplementalData: Segregation and sequencing data shown in Figures 1 and 4
Patient 3, a 37-year-old Caucasian woman, presented in July 1998 with a gradual decline in visual acuity that began at the age of 12.
Case#: Patient 3, 37-year-old female
PMID: 10612508
DiseaseAssertion: STGD1
FamilyInfo: Affected sibling in autosomal recessive family.
CasePresentingHPOs: HP:0000545 — Decreased visual acuity HP:0007754 — Macular atrophy HP:0030638 — Retinal flecks HP:0000512 — Abnormal fundus morphology
CaseHPOFreeText: Gradual visual decline beginning at age 12. Visual acuity 20/400 in both eyes. Fundus examination revealed bilateral macular atrophy with pigment deposits and numerous yellow flecks in the posterior pole and midperiphery. Fluorescein angiography showed large hypofluorescent regions with surrounding hyperfluorescence and peripheral dark choroid.
CaseNotHPOs: Not reported
CaseNotHPOFreeText: Not reported
GenotypingMethod: PCR and direct sequencing of ABCA4
PreviouslyPublished: Yes
Variant: NM_000350.2:c.2588G>C (p.Gly863Ala) NM_000350.2:c.161G>A (p.Cys54Tyr)
ClinVar: Not reported
CAID: Not reported
SupplementalData: Segregation and sequencing data (Figures 1, 4)
Quantifying fixation in patients with Stargardt disease
PMID: 17562343 GeneName: ABCA4
Phenotype/genotype correlation in a case series of Stargardt's patients identifies novel mutations in the ABCA4 gene
PMID: 23949494 HGNC: 34 Gene: ABCA4 DiseaseAssertion: Stargardt Disease