Case#: Xin_Patient_6, sex not mentioned, age 8 at onset, Swedish nationality

CasePresentingHPOs: HP:0004302 (Functional motor deficit), HP:0000572 (Visual loss), HP:0001250 (Seizure), HP:0001268 (Mental deterioration), HP:0003621 (Juvenile onset), HP:0003208 (Fingerprint intracellular accumulation of autofluorescent lipopigment storage material), HP:0003205 (Curvilinear intracellular accumulation of autofluorescent lipopigment storage material)

CaseHPOFreeText: Motor difficulty was the phenotype at presentation (age 8). Seizures (age 8), Visual loss (age 12), and Cognitive regression (age 11) subsequently developed. Curvilinear inclusions were observed in the skin specifically.

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 harbors the NM_006493.4(CLN5):c.78G>A (p.Trp26Ter) and NM_006493.4(CLN5):c.522dup (p.Trp175LeufsTer30) variants, as well as the likely benign NM_006493.4(CLN5):c.381T>G (p.Thr127=) variant.

ClinVar: 2565, 56543, 128783

gnomAD: Maximum allele frequency for NM_006493.4(CLN5):c.78G>A (p.Trp26Ter) is 0.00005132 (in the European non-Finnish population, no homozygotes). https://gnomad.broadinstitute.org/variant/13-77566311-G-A Maximum allele frequency for NM_006493.4(CLN5):c.522dup (p.Trp175fs) is 0.00007033 (in the European non-Finnish population, no homozygotes). Maximum allele frequency for the NM_006493.4(CLN5):c.381T>G (p.Thr127=) variant is 0.06570 (in the East Asian population, 48 homozygotes) https://gnomad.broadinstitute.org/variant/13-77570078-T-G

VariantEvidence: The NM_006493.4(CLN5):c.78G>A (p.Trp26Ter) nonsense variant is likely to be subject to nonsense mediated decay. The NM_006493.4(CLN5):c.522dup (p.Trp175fs) frameshift variant is predicted to truncate ~51% of the protein. On the other hand, the synonymous NM_006493.4(CLN5):c.381T>G (p.Thr127=) variant appears unlikely to have a gene impact.

CaseAddInfo: Parents do not appear to have been genotyped, so it is unclear whether the two variants with predicted gene impact have been shown or simply assumed to be in trans. The same is true for the benign, synonymous variant.

CasePMIDs: N/A

Case#: Brandl_2017_Family_13-501_Proband_#1, male, age 13 years at time of report, national origin reported as German

CasePresentingHPOs: HP:0007677 (Vitelliform-like macular lesions), HP:0007663 (Reduced visual acuity, 0.1 to 0.2 logMAR), HP:0007703 (Abnormality of retinal pigmentation, particularly in the center), HP:0000493 (Abnormal foveal morphology, specifically foveal detachment)

CaseHPOFreeText: The patient has been diagnosed with vitelliform macular dystrophy with onset in early childhood. The abnormal foveal morphology refers specifically to foveal detachment.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous testing appears to have been limited to Sanger sequencing of the BEST1 and PRPH2 loci.

CaseMethod1: Sanger sequencing of the exons and flanking intronic sequences of IMPG1 and IMPG2.

CaseMethod2: N/A

CaseGenotypingMethod: Previous testing appears to have been limited to Sanger sequencing of the BEST1 and PRPH2 loci, while subsequent genotyping included Sanger sequencing of the exons and flanking intronic sequences of IMPG1 and IMPG2.

Variant: The proband harbors the NM_001563.4(IMPG1):c.713T>C (p.Leu238Pro) variant in the heterozygous state.

ClinVar: 865770

gnomAD: The NM_001563.4(IMPG1):c.713T>C (p.Leu238Pro) variant was found in gnomAD v2.1.1 at a frequency of 0.00006598 (2/30310) in the South Asian population, with 0 homozygotes https://gnomad.broadinstitute.org/variant/6-76728530-G-A?dataset=gnomad_r2_1

VariantEvidence: NM_001563.4(IMPG1):c.713T>C (p.Leu238Pro) is a missense variant that does not have evidence confirming an impact on the gene product. However, it has been reported by an independent group of researchers in multiple families with vitelliform macular dystrophy (PMID: 23993198).

CaseAddInfo: The proband is the only family member affected, with clinical and genetic testing data on the parents unavailable.

CasePMIDs: N/A

Case: Lin_2006_Family_1_patient_IV-8, female, 62 years of age at presentation, Eastern European Jewish ancestry

DiseaseAssertion: Sorsby's fundus dystrophy

FamilyInfo: N/A

CasePresentingHPOs: HP:0007663 (Reduced visual acuity), HP:0012508 (Metamorphopsia), HP:0011510 (Drusen), HP:0025148 (Dark choroid), HP:0011506 (Choroidal neovascularization), HP:0025094 (Disciform macular scar), HP:0000662 (Nyctalopia), HP:0007703 (Abnormality of retinal pigmentation),

CaseHPOFreeText: Patient presented with central visual field loss and metamorphopsia in one eye, 10 years after a normal results from fundus and vision exam. Fluorescein angiography of the other eye revealed drusen and dark choroid. Choroidal neovascularization progressed to a central disc-shaped scar despite several treatments with argon laser thermal photocoagulation. The less affected eye initially showed mild nyctalopia only, but progressed within 2 years to fibrovascular pigment epithelial detachment, circular blocking lesion, choroidal neovascularization, and visual acuity loss.

CaseNOTHPOs: N/A

CaseNOTHPOFreeText: N/A

CasePreviousTesting: Complete ophthalmological exam to define clinical features.

CaseGenotypingMethod: Bidirectional Sanger sequencing of PCR products from exons 1 through 5.

PreviouslyPublished: N/A

SupplementalData: N/A

Variant: NM_000362.5(TIMP3):c.542A>G, p.His181Arg is a missense variant predicted to replace a conserved histidine residue in exon 5 with arginine (conservative substitution).

CAID: CA411540357

gnomAD: Variant is absent from gnomAD.

VariantEvidence: p.His181Arg is a missense variant predicted to replace a conserved histidine residue in exon 5 with arginine (conservative substitution). Molecular modeling predicts that the affected amino acid is located on a protein-protein interaction interface.

Case#: Gu_1997_Family_PMK18_Patient_V-1, male, unknown age, Indian ethnicity

CasePresentingHPOs: HP:0410280 (Pediatric onset), HP:0007663 (Reduced visual acuity), HP:0001098 (Abnormal fundus morphology)

CaseHPOFreeText: Onset is early and course of disease is severe. The appearance of the fundus in adulthood is considered characteristic of retinitis pigmentosa.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous testing consisted of linkage analysis using microsatellite repeat markers (D152803, DJS1665, D1S438 and DJS1728) associated with the RPE65 locus.

CaseMethod1: Linkage analysis

CaseMethod2: PCR products were screened by restriction digest analysis using the Msel endonuclease.

CaseGenotypingMethod: The patient sample was subjected to PCR and Sanger sequencing of all RPE65 exons.

Variant: 4 out of 5 affected individuals are homozygous for the NM_000329.3(RPE65):c.858+1G>T variant.

ClinVar: 98893

gnomAD: The NM_000329.3(RPE65):c.858+1G>T variant is not shown in gnomAD.

VariantEvidence:

CaseAddInfo: The family pedigree shows consanguinity in the parents of all affected individuals. One of the affected individuals is a heterozygous carrier of the variant, rather than a homozygote.

CasePMIDs: N/A

Case#: Hull_2016_Patient_1.2, male, 18 years of age at onset, Irish ancestry

CasePresentingHPOs: HP:0003581 (Adult onset), HP:0007663 (Reduced visual acuity), HP:0000533 (Chorioretinal atrophy), HP:0000662 (Nyctalopia), HP:0007722 (Retinal pigment epithelial atrophy), HP:0000533 (Chorioretinal atrophy), HP:0030602 (Abnormal fundus autofluorescence imaging), HP:0000510 (Rod-cone dystrophy), HP:0008179 (Decreased Arden ratio of electrooculogram), HP:0000512 (Abnormal electroretinogram)

CaseHPOFreeText: The patient presented at age 18 with nyctalopia, progressed to central visual disturbance at age 33, and was limited to hand movement vision by age 48, with preserved peripheral vision.

CaseNotHPOs: HP:0003593 (Infantile onset), HP:0011463 (Childhood onset)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Variants in REP1 and PRPH2 were initially excluded.

CaseMethod1: Candidate gene sequencing

CaseMethod2: Bidirectional, targeted Sanger sequencing within the RPE65 locus

CaseGenotypingMethod: Bidirectional Sanger sequencing of exon 13 of the RPE65 gene and flanking sequences

Variant: The patient harbors the NM_000329.3(RPE65):c.1430A>G (p.Asp477Gly) variant in one allele of RPE65.

ClinVar: 750796

gnomAD: The NM_000329.3(RPE65):c.1430A>G (p.Asp477Gly) variant was not found in gnomAD.

VariantEvidence: Exogenous expression of the variant reveals protein expression levels, cellular localization and retinoid isomerase activity comparable to the wild-type (PMID: 29659842). However, knock-in mouse models exhibit retinyl ester accumulation (PMID: 29659842), abnormally slow regeneration of 11-cis-retinal after light exposure, and ERG results indicative of delayed dark adaptation (PMID: 28041994). Mice with CRISPR-mediated knock-in of the variant also exhibit a splicing defect in RPE65 due to the introduction of a cryptic splice site, which likely triggers a frameshift, exclusion of exons 13 and 14 from the transcript, and premature truncation of the protein product (PMID: 30628748).

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Yzer_2006_Patient_22597, female, diagnosed soon after birth, family origin not described

CasePresentingHPOs: HP:0003593 (Infantile onset), HP:0006934 (Congenital nystagmus), HP:0030532 (Visual acuity test abnormality), HP:0007843 (Attenuation of retinal blood vessels), HP:0000550 (Undetectable electroretinogram)

CaseHPOFreeText: The individual is described as having Leber congenital amaurosis. Diagnosis was made soon after birth, but an exact age is not described. Visual acuity was limited to light perception.

CaseNotHPOs: HP:0000543 (Optic disc pallor), HP:0007703 (Abnormality of retinal pigmentation)

CaseNotHPOFreeText: Most recent fundus examination was relatively normal at 25 years of age.

CasePreviousTesting: An LCA-specific microarray ChIP was used for initial genotyping, using antisense oligos to screen for 301 known disease-associated variants 6 LCA genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) and two early-onset RP genes (LRAT and MERTK).

CaseMethod1: Sanger sequencing of PCR products from the relevant exon of GUCY2D.

CaseMethod2: N/A

CaseGenotypingMethod: The individual was initially screened using an LCA-specific microarray ChIP with antisense oligos to detect 301 known disease-associated variants 6 LCA genes (AIPL1, CRB1, CRX, GUCY2D, RPE65, and RPGRIP1) and two early-onset RP genes (LRAT and MERTK). Subsequent genotyping was performed by Sanger sequencing of PCR products from the relevant exon of the GUCY2D locus.

Variant: The individual is homozygous for the NM_000180.4(GUCY2D):c.1694T>C (p.Phe565Ser) variant.

ClinVar: 9350

gnomAD: The NM_000180.4(GUCY2D):c.1694T>C (p.Phe565Ser) variant exhibits a maximum allele frequency of 0.000008790 in gnomAD version 2.1.1 (in the European non-Finnish population, with no homozygotes). https://gnomad.broadinstitute.org/variant/17-7912849-T-C?dataset=gnomad_r2_1

VariantEvidence: PMID: 9888789 provides evidence supporting the pathogenicity of the NM_000180.4(GUCY2D):c.1694T>C (p.Phe565Ser) variant by showing that the orthologous bovine F514S point mutation severely decreases the intrinsic cyclase activity of the protein and inactivates one of its calcium-responsive activating switches, CRM1.

CaseAddInfo: Parents were reported to be consanguineous. Segregation / phasing of two variants was not confirmed by parental genotyping.

CasePMIDs: N/A

Case#: Chatterjee_2022_proband_II:4, female, age 16 years at time of report, onset in second decade of life, geographic origin reported as north Indian

CasePresentingHPOs: HP:0410280 (Pediatric onset), HP:0000613 (Photophobia), HP:0000662 (Nyctalopia), HP:0030564 (Best corrected visual acuity 1.1 LogMAR), HP:0025147 (Beaten bronze macular sheen), HP:0011507 (Macular flecks), HP:0030619 (Reduced OCT-measured foveal thickness), HP:0025010 (Foveal atrophy)

CaseHPOFreeText: The patient and siblings have been diagnosed with Stargardt-like juvenile macular dystrophy.

CaseNotHPOs: HP:0007737 (Bone spicule pigmentation of the retina)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of whole-exome sequencing.

CaseMethod1: whole-exome sequencing

CaseMethod2: Sanger sequencing of the 19 exons of the IMPG2 gene

CaseGenotypingMethod: Genotyping consisted of whole-exome sequencing followed by Sanger sequencing of the 19 exons of the IMPG2 gene.

Variant: The patient harbors the NM_016247.4:c.1239+1G>T variant in the homozygous state.

CAID: CA353864391

gnomAD: The variant was found in gnomAD v2.1.1.

VariantEvidence: NM_016247.4:c.1239+1G>T is a canonical splice site variant in intron 11 of the 19-exon locus that has been shown by mini-gene assay to trigger a splicing defect that leads to complete skipping of exon 11. Because this would lead to a shift of frame, the variant is predicted to lead to a premature stop after codon 385 and either NMD or truncation of 69% of the C-terminus of the protein product.

CaseAddInfo: The family is consanguineous, with the parents being first cousins and heterozygous carriers of the variant. The patient has two affected siblings who share the same genotype.

CasePMIDs: N/A

Case: Naessens_2019_Family_2_Patient_II:1, female, age of onset 53 years old, country of origin France (northern)

DiseaseAssertion: Sorsby's fundus dystrophy

FamilyInfo: Familial variant appears to come from a founder mutation shared by other families in Belgium and northern France with a distant common ancestor.

CasePresentingHPOs: HP:0011510 (Drusen), , HP:0000572 (Visual loss), HP:0007401 (Macular atrophy), HP:0007769 (Peripheral retinal degeneration), HP:0011506 (Choroidal neovascularization), HP:0007777 (Chorioretinal scar)

CaseHPOFreeText: Relatively late onset of phenotypes (at age 53, presenting with nyctalopia). Drusen was described as widespread and partially calcified. Macular atrophy was patchy, with round atrophic patches outside the vascular arcades.

CaseNOTHPOs: N/A

CaseNOTHPOFreeText: Pulmonary involvement

CasePreviousTesting: N/A

GenotypingMethod: PCR amplification of all 5 coding exons of TIMP3, followed by Sanger sequencing

PreviouslyPublished: N/A

SupplementalData: Supplementary Table S3 from this paper (PMID: 30668888) provides some of the proband phenotype details.

Variant: The variant is NM_000362.5(TIMP3):c.113C>G (p.Ser38Cys), a missense variant predicted to introduce a new cysteine-encoding codon into exon 1.

ClinVar: 843268

gnomAD: Variant is absent from gnomAD.

VariantEvidence: Variant adds a Cys residue to TIMP3 and is predicted to disrupt tertiary structure. Patient fibroblasts reveal no change in expression of the variant at the mRNA level, no dimerization of the variant under non-reducing conditions, and no defect in its localization to the ECM. Variant showed a minor increase in glycosylation. An in vitro transcription and translation study found that the variant forms an aberrant intramolecular disulfide bond between the introduced Ser38Cys residue and Cys36 of TIMP3 (Figure 7). Aberrant intramolecular disulfide bonding caused by this variant would be consistent gain-of-function and an autosomal dominant mechanism of inheritance.

Case#: Bessa_Patient_1, female, age 3 at onset, Portuguese nationality

CasePresentingHPOs: HP:0000736 (Short attention span), HP:0002463 (Language impairment), HP:0002312 (Clumsiness), HP:0033044 (Motor regression), HP:0002376 (Developmental regression), HP:0000572 (Visual loss), HP:0002066 (Gait ataxia), HP:0001336 (Myoclonus), HP:0010819 (Atonic seizure), HP:0032794 (Myoclonic HP:0000648 (Optic atrophy), HP:0000546 (Retinal degeneration), HP:0012011 (EEG with occipital focal spike waves), HP:0002059 (Cerebral atrophy), HP:0001272 (Cerebellar atrophy), HP:0030891 (Periventricular white matter hyperdensities), HP:0001268 (Mental deterioration), HP:0031058 (Impairment of activities of daily living), HP:0011463 (Childhood onset), HP:0000712 (Emotional lability), HP:0002015 (Dysphagia), HP:0010864 (Intellectual disability, severe), HP:0001332 (Dystonia), HP:0007256 HP:0025357 (Erratic myoclonus), HP:0003205 (Curvilinear intracellular accumulation of autofluorescent lipopigment storage material), HP:0003208 (Fingerprint intracellular accumulation of autofluorescent lipopigment storage material)

CaseHPOFreeText: Progressive attention deficits and regression of language ability were the phenotypes at presentation (age 3). Motor clumsiness presented at age 4, initiating a larger pattern of developmental regression. Phenotypes with onset at age 7 included visual deterioration, gait ataxia, distal and axial myoclonus, atonic and myoclonic generalized epileptic seizures, bilateral optic atrophy, retinal degeneration, abnormal EEG showing diffuse slowing of background rhythm and occipital spike-wave activity, and abnormal brain MRI with cerebral and cerebellar atrophy as well as increased signal intensity of both the posterior limb of the capsula interna and the periventricular white matter. At age 8, any independence in daily activities was lost, as well as any language abilities. Ataxic gait was marked, and EEG activity showed slowing and disorganization, frequent multifocal high-voltage polyspike-slow wave complexes, and epileptic activity corresponding to myoclonus. At 15 years (time of study), the patient was bedridden and showed amaurotic behavior, emotional lability, marked dysphagia, severe mental retardation, dystonic postures of the limbs and trunk, pyramidal signs in the limbs, bilateral optic atrophy, and frequent myoclonus (both erratic and stimulus-induced). Intracellular accumulation of autofluorescent lipopigment storage material was also detected at age 15.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotype testing was not performed. While the PPT1 and TPP1 loci were not sequenced, their enzymatic activity in extracts from leucocyte and fibroblast cells was confirmed to be within the normal range.

CaseGenotypingMethod: Based on detailed clinical phenotypes consistent with variant NCL with late-infantile onset, coding regions and intron boundaries of the CLN3, CLN5, and CLN6 loci were PCR-amplified and subjected to Sanger sequencing. Genome-wide analysis methods were not used. Parents (and patient) were subsequently genotyped using single strand conformational polymorphisms and restriction digest of PCR products, to identify variants in cis and in trans with one another.

Variant: The patient is a compound heterozygote with a paternally inherited NM_006493.4(CLN5):c.418C>T (p.Gln140Ter) variant and maternally inherited NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) and NM_006493.4(CLN5):c.188G>C (p.Arg63Pro) variants.

ClinVar: 56538, 2566, 56533

gnomAD: The maximum allele frequency of the NM_006493.4(CLN5):c.688G>A (p.Asp230Asn) variant is 0.00005437 (within the East Asian population, with no homozygous occurrences). https://gnomad.broadinstitute.org/variant/13-77574715-G-A The NM_006493.4(CLN5):c.418C>T (p.Gln140Ter) and NM_006493.4(CLN5):c.188G>C (p.Arg63Pro) variants are absent from gnomAD.

VariantEvidence: Reduced CLN5 expression by 45% at the mRNA level indicates that one of the two alleles may be subject to nonsense mediated decay and likely absence of the corresponding protein product. This may confirm the prediction that the nonsense variant NM_006493.4(CLN5):c.418C>T (p.Gln140Ter) is likely subject to nonsense mediated decay. One of the two maternally inherited variants, NM_006493.4(CLN5):c.688G>A (p.Asp230Asn), has been previously shown to introduce an additional N-glycosylation site within the C-terminal region of CLN5 (PMID:20052765) and to disturb its localization to the lysosome (PMID:20052765).

CaseAddInfo: Parents are healthy and non-consanguineous.

CasePMIDs: N/A

Case#: Morimura_1998_Family_9145_Patient_II-1, female, age and family origin not specified

CasePresentingHPOs: HP:0000546 (Retinal degeneration)

CaseHPOFreeText: While specific phenotypes are not provided, the initial diagnosis of Leber congenital amaurosis indicates that the proband was either born blind or lost vision within a period of months after birth.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: All 14 RPE65 exons and flanking sequences were PCR-amplified and subjected to single-strand conformation polymorphism analysis (SSCA).

CaseMethod1: Screening of PCR-amplified RPE65 exons using SSCA

CaseMethod2: Sanger sequencing of all 14 exons of RPE65

CaseGenotypingMethod: PCR-amplified exons identified by SSCA as candidates to harbor variants were subjected to Sanger sequencing.

Variant: The proband is a homozygote within the RPE65 locus, harboring the NM_000329.3(RPE65):c.1418T>A (p.Val473Asp) variant.

ClinVar: 98846 (homozygous)

gnomAD: The NM_000329.3(RPE65):c.1418T>A (p.Val473Asp) variant is not found within gnomAD.

VariantEvidence: NM_000329.3(RPE65):c.1418T>A (p.Val473Asp) is a missense variant with unknown impact on gene function.

CaseAddInfo: While the variant is known to be homozygous, the proband's parents have not been genotyped. The potential consanguinity of the parents was not mentioned.

CasePMIDs: N/A

Case#: Morimura_1998_Family_7828_Patient_III-4, male, age not specified, from family originating in the Dominican Republic

CasePresentingHPOs: HP:0000546 (Retinal degeneration)

CaseHPOFreeText: While specific phenotypes are not provided, the diagnosis of retinitis pigmentosa indicates that the affected family members maintained central vision during the first decade of life and subsequently experienced severe vision loss.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: All 14 RPE65 exons and flanking sequences were PCR-amplified and subjected to single-strand conformation polymorphism analysis (SSCA).

CaseMethod1: Screening of PCR-amplified RPE65 exons using SSCA

CaseMethod2: Sanger sequencing of all 14 exons of RPE65

CaseGenotypingMethod: PCR-amplified exons identified by SSCA as candidates to harbor variants were subjected to Sanger sequencing.

Variant: The proband is a compound heterozygote harboring the NM_000329.3(RPE65):c.1022T>C (p.Leu341Ser) and NM_000329.3(RPE65):c.1207_1210dup (p.Glu404fs) variants.

ClinVar: 13118, 98831

gnomAD: Neither the NM_000329.3(RPE65):c.1022T>C (p.Leu341Ser) variant nor the NM_000329.3(RPE65):c.1207_1210dup (p.Glu404fs) variant is found within gnomAD.

VariantEvidence: The paternal frameshift variant is predicted to either trigger NMD or disrupt 24% of the protein product. The maternal missense variant does not have evidence of gene impact.

CaseAddInfo: The two variants were confirmed to be in trans, and heterozygous carriers were found to be unaffected. Potential consanguinity between the parents was not reported, at least within the first generation of the pedigree.

CasePMIDs: N/A

Case#: Li_2025_Proband_XXXVII, age 8 years at time of report, male, seen at a medical center in Beijing

CasePresentingHPOs: Abnormal morphology of the choroidal vasculature HP:0025568, High myopia HP:0011003, Best corrected visual acuity 0.1 LogMAR HP:0030554

CaseHPOFreeText: The choroidal vascular abnormality referred to in the text was described as a tesselated fundus. The patient's refractive error was reported as -14.00 and -12.88 in the two eyes, with, axial lengths of 27.01 and 26.64.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by whole genome sequencing.

CaseMethod1: whole genome sequencing

CaseMethod2: possibly Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by whole genome sequencing, possibly followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.843G>A (p.Trp281Ter) variant in the hemizygous state.

CAID: CA415308527

gnomAD: The variant is found in gnomAD version 4.1.0 at a frequency of 0.00002111 (1 / 47,376) in the Remaining population. https://gnomad.broadinstitute.org/variant/chrX-154156392-G-A?dataset=gnomad_r4

VariantEvidence: NM_020061.6(OPN1LW):c.843G>A (p.Trp281Ter) is a nonsense variant in exon 5 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Beijing.

CasePMIDs: N/A

Case#: Family_22142_Proband_II-1, onset before age 7 years, male, seen at a medical center in Guangzhou

CasePresentingHPOs: High myopia HP:0011003, Blurred vision HP:0000622, Childhood onset HP:0011463, Protanopia HP:0011522

CaseHPOFreeText: The proband is part of a cohort in which all patients had a diagnosis of early onset high myopia, with onset in early childhood and either high myopia or axial length >25 mm before age 7, or refractive errors <-10 as an adult.

CaseNotHPOs: Nystagmus HP:0000639, Photophobia HP:0000613, Nyctalopia HP:0000662

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing.

CaseMethod1: targeted exome or whole exome sequencing

CaseMethod2: Sanger sequencing of OPN1LW

CaseGenotypingMethod: Genotyping of the proband was performed by either targeted exome sequencing or whole exome sequencing, followed by Sanger sequencing of OPN1LW.

Variant: The individual harbors the NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter) variant in the hemizygous state.

ClinVarID: 10503

gnomAD: The variant was not found in gnomAD version 4.1.0.

VariantEvidence: NM_020061.6(OPN1LW):c.739C>T (p.Arg247Ter) is a nonsense variant in exon 3 of 6 that is predicted to undergo nonsense-mediated decay.

CaseAddInfo: The proband was seen at a medical center in Guangzhou. The variant was inherited from the proband's unaffected mother.

CasePMIDs: N/A

Case#: van_Dorp_1992_Family_P9145_patient_IV-20, male, age not reported, family origin reported to be Dutch

CasePresentingHPOs: HP:0012263 (Immotile cilia), HP:0002205 (Recurrent respiratory infections), HP:0012261 (Abnormal respiratory motile cilium physiology), HP:0012255 (Dynein arm defect of respiratory motile cilia), HP:0012260 (Abnormal central microtubular pair morphology of respiratory motile cilia), HP:0012864 (Abnormal sperm morphology),

CaseHPOFreeText: The proband has been diagnosed with retinitis pigmentosa in combination with recurrent respiratory infections. The family exhibits an X-linked pattern of inheritance. Inner dynein arms of respiratory cilia were described as deficient. Cilia were described as disoriented.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The patient and his family members were subjected to linkage analysis using X chromosomal markers, followed by a chromosomal analysis of the patient that revealed no abnormalities (such as a translocation involving the X chromosome).

CaseMethod1: Linkage analysis (PMID: 1733835)

CaseMethod2: Sanger sequencing of PCR products from the RPGR locus (PMID: 10094550)

CaseGenotypingMethod: The patient and family members were subjected to linkage analysis using X chromosomal markers, and then the patient DNA underwent chromosomal analysis that revealed no abnormalities (such as a translocation involving the X chromosome). The family members were then genotyped by Sanger sequencing of PCR products from the RPGR locus (PMID: 10094550).

Variant: The patient harbors the NM_001034853.2(RPGR):c.469+1G>T variant in the hemizygous state.

ClinVar: 9912

gnomAD: The variant was not found in gnomAD v.2.1.1.

VariantEvidence: NM_001034853.2(RPGR):c.469+1G>T is a canonical splice site variant in the final exon (exon 15) that disrupts the 5' splice site of intron 5. Functional evidence confirming the expected effect on splicing is not available.

CaseAddInfo: The proband is a member of Family P9145 (shown in Figure 1), which includes four other affected genotype-positive males and as well as three carrier females who showed no detectable abnormality. The detailed genotype for the affected and carrier individuals was later published in PMID: 10094550.

CasePMIDs: PMID: 10094550

Case#: Bin_2009_Family_04-01_Case_26, female, age 11.6 years at time of report, national origin reported as from Peru

CasePresentingHPOs: HP:0001513 (Obesity), HP:0010442 (Polydactyly), HP:0100543 (Cognitive impairment), HP:0012758 (Neurodevelopmental delay), HP:0003077 (Hyperlipidemia), HP:0034685 (Abnormal liver enzyme activity or concentration), HP:0000077 (Abnormality of the kidney), HP:0410042 (Abnormal liver morphology), HP:0030515 (Moderately reduced visual acuity), HP:0000548 (Cone/cone-rod dystrophy), HP:0001133 (Constriction of peripheral visual field)

CaseHPOFreeText: The patient has been diagnosed with Bardet-Biedl syndrome.

CaseNotHPOs: HP:0000639 (Nystagmus), HP:0000518 (Cataract)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of Sanger sequencing of the TTC8 locus.

CaseMethod1: Sanger sequencing of the TTC8 locus

CaseMethod2: Sanger sequencing of the BBS7 locus

CaseGenotypingMethod: Genotyping consisted of Sanger sequencing of the TTC8 and BBS7 loci.

Variant: The patient harbors the NM_176824.3:c.712_715del (p.Arg238GlufsTer?) and NM_176824.3:c.1121C>G (Ser374Ter) variants in the compound heterozygous state.

CAID: CA3064432, CA358062298

gnomAD: The NM_176824.3:c.1121C>G (Ser374Ter) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0001633 (1/6124 in the Other population), with 0 homozygotes. https://gnomad.broadinstitute.org/variant/4-122766768-G-C The NM_176824.3:c.712_715del (p.Arg238GlufsTer?) variant is found in gnomAD v2.1.1 at a maximum allele frequency of 0.0001146 (13/113390) in the European non-FInnish population), with 0 homozygotes.

VariantEvidence: NM_176824.3:c.1121C>G (Ser374Ter) is a nonsense variant in exon 11 of 18 that is predicted to trigger nonsense-mediated decay or at least truncation of the C-terminal 48% of the protein product. NM_176824.3:c.712_715del (p.Arg238GlufsTer?)is a frameshift variant in exon 7 of 18 that is predicted to trigger nonsense-mediated decay or at least truncation of the C-terminal 67% of the protein product.

CaseAddInfo: Consanguinity in the proband's family has not been reported. The carrier status of her unaffected parents and an unaffected sibling have been confirmed by genotyping.

CasePMIDs: N/A

Case#: Preising_2001_Patient_IV.1, male, age 3 months at time of diagnosis, family ethnicity described as White

CasePresentingHPOs: HP:0006934 (Congenital nystagmus), HP:0012805 (Iris transillumination defect), HP:0007894 (Hypopigmentation of the fundus), HP:0001104 (Macular hypoplasia), HP:0007663 (Reduced visual acuity), HP:0030463 (Asymmetrical distribution of flash visual evoked potentials), HP:0025551 (Optic nerve misrouting)

CaseHPOFreeText: The proband and his family members have been diagnosed with congenital nystagmus.

CaseNotHPOs: HP:0009887 (Abnormality of hair pigmentation), HP:0001000 (Abnormality of skin pigmentation)

CaseNotHPOFreeText: N/A

CasePreviousTesting: The patients were initially genotyped by SSCP of PCR products from each exon, revealing an abnormality in exon 6.

CaseMethod1: SSCP

CaseMethod2: Sanger sequencing

CaseGenotypingMethod: The proband was initially genotyped by SSCP of PCR products from each exon, revealing an abnormality in exon 6, followed by Sanger sequencing and restriction enzyme analysis by Tsp509I digest of PCR products from all family members.

Variant: The proband harbors the NM_000273.3(GPR143):c.756_767+2del variant in the hemizygous state.

ClinVar: 98643

gnomAD: This variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_000273.3(GPR143):c.756_767+2del is a 14-bp deletion variant removing the 3' end of exon 6 and the canonical splice donor site, and has been shown to trigger aberrant splicing that leads to frameshift at codon 252 and premature termination at codon 259 (Figure 4C).

CaseAddInfo: The proband is part of a family with at least 3 affected generations showing a pattern of X-linked inheritance, including a similarly affected maternal uncle.

CasePMIDs: N/A

Case#: Zhou_2008_Patient_III:22, male, age of onset not reported, family origin reported to be from China

CasePresentingHPOs: HP:0000639 (Nystagmus), HP:0000646 (Amblyopia)

CaseHPOFreeText: The proband has been diagnosed with congenital nystagmus.

CaseNotHPOs: HP:0040030 (Chorioretinal hypopigmentation)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Genotyping was initially performed by linkage mapping using 26 short tandem repeat markers on the X chromosome.

CaseMethod1: linkage analysis

CaseMethod2: Sanger sequencing

CaseGenotypingMethod: Genotyping was initially performed by linkage mapping using 26 short tandem repeat markers on the X chromosome, followed by Sanger sequencing of PCR products from each exon of the GPR143 gene.

Variant: The proband harbors the NM_000273.3(GPR143):c.162_198del (p.Ala55fs) variant in the hemizygous state.

ClinVar: 10524

gnomAD: This variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_000273.3(GPR143):c.162_198del (p.Ala55fs) is a frameshift variant in exon 1, and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 87% of the protein product.

CaseAddInfo: The proband is from a family with at least seven other affected males who also harbor the variant.

CasePMIDs: N/A

Case#: Fang_2008_Family_1_Patient_IV16, male, age 8 at time of report, family national origin reported to be from China

CasePresentingHPOs: HP:0000639 (Nystagmus), HP:0030534 (Abnormal best corrected visual acuity test), HP:0007750 (Hypoplasia of the fovea)

CaseHPOFreeText: The proband and his affected family members have been diagnosed with ocular albinism 1.

CaseNotHPOs: HP:0007730 (Iris hypopigmentation), HP:0007894 (Hypopigmentation of the fundus)

CaseNotHPOFreeText: albinotic fundus

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing

CaseMethod2: N/A

CaseGenotypingMethod: The proband was genotyped by Sanger sequencing of PCR products from the 9 exons of the GPR143 gene.

Variant: The proband harbors the NM_000273.3(GPR143):c.849del (p.Val284SerfsTer15) variant in the hemizygous state.

CAID: CA2573320706

gnomAD: This variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_000273.3(GPR143):c.849del (p.Val284SerfsTer15) is a frameshift variant in exon 7 of 9, predicted to trigger nonsense-mediated decay or to at least truncate 30% of the protein product.

CaseAddInfo: The family of the proband includes at least 7 other affected males and 4 unaffected female carriers.

CasePMIDs: N/A

Case#: Savukoski_Fin_Minor_Patient_1, no demographic details, Finnish origin

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous testing relied on linkage analysis using PCR-amplifiable polymorphisms, including microsatellite markers. The marker D13S160 was found to co-segregate with disease with a LOD score of 4.78 across 14 Finnish pedigrees, mapping the disease locus to chromosome 13q21.1-q32 (PMID:7942847). A follow-up study used two additional microsatellite markers to map the locus to a 200-kb region (PMID:8661106), which was then analyzed in the present study and found to contain a single coding gene.

CaseMethod1: Linkage analysis using PCR-amplifiable polymorphisms, including microsatellite markers, followed by more detailed linkage analysis using two additional microsatellite markers to map the locus to a smaller 200-kb region (PMID:8661106).

CaseMethod2: N/A

CaseGenotypingMethod: PCR products from the four exons of CLN5 were generated from the affected individual and a control individual and subjected to Sanger sequencing. Genome-wide analysis methods were not used.

Variant: Patient is homozygous for NM_006493.4(CLN5):c.78G>A (p.Trp26Ter), although this variant is referred to in the article as c.G1517A or p.Trp75Stop.

ClinVar: 2565

gnomAD: The variant is reported to have a maximum allele frequency of 0.00005132 (in the European non-Finnish population, with no homozygous individuals). https://gnomad.broadinstitute.org/variant/13-77566311-G-A

VariantEvidence: This nonsense variant is predicted to introduce a stop codon near the N-terminus of the encoded protein, likely triggering NMD and the absence of a protein product (loss of function).

CaseAddInfo: N/A

CasePMIDs: PMID:7942847, PMID:8661106

Case#: Weisschuh_2020_Patient_ARRP_339, male, age 32 years at diagnosis, age 34 years at report, national origin reported as German

CasePresentingHPOs: N/A

CaseHPOFreeText: The patient has been diagnosed with autosomal recessive retinitis pigmentosa.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous genotyping consisted of next generation sequencing-based RET.8 panel.

CaseMethod1: next generation sequencing-based RET.8 panel

CaseMethod2: N/A

CaseGenotypingMethod: Genotyping was performed using a next-generation sequencing-based RET.8 panel.

Variant: The patient harbors the NM_001563.4(IMPG1):c.1291+1G>T variant in the homozygous state.

ClinVar: 547007

gnomAD: The NM_001563.4(IMPG1):c.1291+1G>T variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_001563.4(IMPG1):c.1291+1G>T is a canonical splice site variant in intron 12 of the 17-exon locus, and does not have evidence of impact on the protein product.

CaseAddInfo: Segregation confirmation in family members is not available.

CasePMIDs: N/A

Case#: Mykykyn_2002_Proband_PR3-1, 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.1645G>T (p.Glu549Ter) and NM_024649.5(BBS1):c.1169T>G (p.Met390Arg) variants in the compound heterozygous state.

ClinVar ID: 12144, 12143

gnomAD: The NM_024649.5(BBS1):c.1645G>T (p.Glu549Ter) variant is found in gnomAD v2.1.1 at a frequency of 0.00008675 (3 alleles out of 34584 total alleles, with 0 homozygotes) in the Admixed American population https://gnomad.broadinstitute.org/variant/11-66299163-G-T?dataset=gnomad_r2_1 gnomAD: The NM_024649.5(BBS1):c.1169T>G (p.Met390Arg) 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.1645G>T (p.Glu549Ter) is a nonsense variant in exon 16 of 17 that is predicted to not to trigger nonsense-mediated decay but rather to truncate the C-terminal 8% of the protein product. 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 has not been described as consanguineous.

CasePMIDs: N/A

Case#: Dueñas Rey_2024_Proband_F11, sex and age not reported, part of cohort from Center for Medical Genetics Ghent

CasePresentingHPOs: Rod-cone dystrophy HP:0000510, Intellectual disability HP:0001249

CaseHPOFreeText: The proband has been diagnosed with rod-cone dystrophy and clinical signs of Bardet-Biedl syndrome. Intellectual disability may be part of the phenotype.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Previous testing in the proband consisted of whole exome sequencing with analysis focused on the 5' UTR regions of 378 genes highly expressed in the retina.

CaseMethod1: whole exome sequencing

CaseMethod2: Sanger sequencing of the coding regions of PRPF4

CaseGenotypingMethod: Genotyping of the proband initially consisted of whole exome sequencing, followed by Sanger sequencing of the coding regions of PRPF4.

Variant: The proband harbors the NM_001244926.2:c.-6C>T variant in the heterozygous state.

CAID: CA2579423618

gnomAD: The NM_001244926.2:c.-6C>T variant is found in gnomAD v4.1.0 at a frequency of 8.400e-7 (4 alleles / 1178930 total alleles, with 0 homozygotes) in the European (non-Finnish) population https://gnomad.broadinstitute.org/variant/9-113275738-C-T?dataset=gnomad_r4

VariantEvidence: NM_001244926.2:c.-6C>T is a 5' UTR variant located within the Kozak consensus sequence but has no direct evidence of an abnormal impact on PRPF4 expression.

CaseAddInfo: The proband has apparently unaffected parents.

CasePMIDs: N/A

Case#: Zou_2017_Patient_F3-III:3, male, age 24 at time of report, family national origin reported to be from China

CasePresentingHPOs: HP:0000639 (Nystagmus), HP:0000613 (Photophobia), HP:0007663 (Reduced visual acuity), HP:0007750 (Hypoplasia of the fovea), HP:0007894 (Hypopigmentation of the fundus), HP:0007730 (Iris hypopigmentation), HP:0030534 (Abnormal best corrected visual acuity test)

CaseHPOFreeText: The proband has been diagnosed with ocular albinism 1. Foveal hypoplasia was described as severe. Best-corrected visual acuity was limited to light perception.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing

CaseMethod2: N/A

CaseGenotypingMethod: Patients were genotyped by Sanger sequencing of PCR products from the 9 exons of the GPR143 gene.

Variant: The proband harbors the NM_000273.3(GPR143):c.733C>T (p.Arg245Ter) variant in the hemizygous state.

ClinVar: 1352731

gnomAD: This variant was not found in gnomAD v2.1.1.

VariantEvidence: NM_000273.3(GPR143):c.733C>T (p.Arg245Ter) is a nonsense variant in exon 6 of 9, and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 40% of the protein product.

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Wang_2013_Patient_704, female, age 9 years at onset, family origin not reported

CasePresentingHPOs: HP:0007663 (Reduced visual acuity), HP:0000662 (Nyctalopia), HP:0007737 (Bone spicule pigmentation of the retina), HP:0000543 (Optic disc pallor), HP:0007843 (Attenuation of retinal blood vessels), HP:0000822 (Hypertension), HP:0000858 (Irregular menstruation), HP:0025502 (Overweight)

CaseHPOFreeText: The proband has a diagnosis of juvenile retinitis pigmentosa. Visual acuity was limited to hand movements and later to light perception. Patient is described as slightly overweight.

CaseNotHPOs: HP:0000639 (Nystagmus)

CaseNotHPOFreeText: N/A

CasePreviousTesting: The proband was subjected to capture-based next-generation sequencing panel that included 163 known retinal disease genes.

CaseMethod1: next-generation sequencing panel

CaseMethod2: SNP array and Sanger sequencing of BBS1

CaseGenotypingMethod: The proband was genotyped by capture-based next-generation sequencing panel that included 163 known retinal disease genes. SNP array and Sanger sequencing of BBS1 were subsequently used to confirm the presence of 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 variant reportedly segregates with disease within the proband's family, but details are not available.

CasePMIDs: N/A

Case#: RP19, IV-1

CaseHPOs: HP:0007642, HP:0030824 (Congenital stationary night blindness, Mizuo-Nakamura phenomenon)

CaseHPOsFreeText: Diffuse gray discoloration of the fundus, scotopic ERG showed a significantly reduced rod response (in selected individuals analyzed)

CaseNotHPOsFreeText: During fundoscopy of the individuals IV-3 and V-1, no bone spicule deposits were observed in the fundus.

CaseMethod1: PCR

CaseMethod2: Sequencing

CaseGenotypingMethod: All seven coding exons and flanking intronic sequences of GRK1 were sequenced in affected family members IV-1, V-5, and V-11.

Variant: NM_002929.3(GRK1):c.614C>A (p.Ser205Ter) (homozygous)

ClinVar: 870430

CAID: CA388824706

gnomAD: Not in gnomAD

Case#: Uttarilli Patient 6, male, 4yo at presentation

DiseaseAssertion: MPS1, Hurler-Scheie

FamilyInfo: non-consanguineous

CasePresentingHPOs: HP:0007957, HP:0000280, HP:0000943, HP:0002240, HP:0001744

CaseHPOFreeText: IDUA enzyme activity=0 (reference = 11–26 nmol/h/mg)

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: PCR of all exons of IDUA and IDS genes and bidirectional sequencing

PreviouslyPublished:

Variant: [c.223G>A] [p.Ala75Thr]; [c.895G>T] [p.Glu299*]

CAID: CA356994; CA355962511

SupplementalData: n/a

Case#: Patient 25, male, 7 months (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomyopathy, dysostosis multiplex, global developmental delay, hepatomegaly, inguinal hernia, skeletal abnormalities, splenomegaly, recurrent respiratory infections (HP:0007957, HP:0000256, HP:0001638, HP:0000943, HP:0001263, HP:0002240, HP:0000023, HP:0002652, HP:0001744, HP:0002205)

CaseHPOFreeText: Global dyskinesia

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.R619X)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.R619X)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 20, male, 8 years (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family not present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomyopathy, dystosis multiplex (HP:0007957, HP:0000256, HP:0001638, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 16, female, 1 year and 3 months (age at presentation).

DiseaseAssertion: MPS1-H/S

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, cardiomyopathy, dystosis multiplex (HP:0007957, HP:0000256, HP:0001638, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.972-1G>T

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.972-1G>T

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 12, female, 6 months (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dystosis multiplex, hepatomegaly, joint stiffness, intellectual disability, recurrent respiratory infections, splenomegaly, umbilical hernia (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0001387, HP:0010864, HP:0002205, HP:0001744, HP:0001537)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.783delC (p.His262Thrfs*55)

Variant1ClinVarID: 956890

Variant1CAID: CA2802083

Variant2: c.783delC (p.His262Thrfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 26, male, 1 year (age at presentation).

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguinity in the family not present for this patient.

CasePresentingHPOs: Corneal clouding, coarse facial features, dysostosis multiplex, hepatomegaly, intellectual disabilities, splenomegaly (HP:0007957, HP:0000256, HP:0000943, HP:0002240, HP:0010864, HP:0001744)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.R619X)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.R619X)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 47, female, Han origin, 4 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Hepatosplenomegaly, Airway obstruction (HP:0001387, HP:0001433, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hernia (HP:0001263, HP:0000256, HP:0011369, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.9 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: N/A

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.1898C>T (p.S633L)

Variant2ClinVarID: 556406

Variant2CAID: CA355961718

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 57, female, Han origin, 2 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness (HP:0001387)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001263, HP:0000256, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1262T>C (p.L421P)

Variant1ClinVarID: 1328979

Variant1CAID: CA355963724

Variant2: c.1898C>T (p.S633L)

Variant2ClinVarID: 556406

Variant2CAID: CA355966010

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 14, female, Han origin, 5.5 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Hernia (HP:0001387, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hepatosplenomegaly, Airway obstruction (HP:0001263, HP:0000256, HP:0011369, HP:0001433, HP:0006536)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.266G>A (p.R89Q)

Variant1ClinVarID: 11922

Variant1CAID: CA256124

Variant2: c.266G>A (p.R89Q)

Variant2ClinVarID: 11922

Variant2CAID: CA256124

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed by parental testing.

PreviouslyPublished N/A

Case#: Patient 30, male, Han origin, 37 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Airway obstruction (HP:0001387, HP:0006536)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula, Hepatosplenomegaly, Hernia (HP:0001263, HP:0000256, HP:0011369, HP:0001433, HP:0100790)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 2.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.265C>T (p.R89W)

Variant1ClinVarID: 580286

Variant1CAID: CA2801156

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, female, Han origin, 9 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/S

CasePresentingHPOs: Joint stiffness, Mongolian macula, Hepatosplenomegaly, Airway obstruction (HP:0001387, HP:0011369, HP:0001433, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Hernia (HP:0001263, HP:0000256, HP:0100790)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 3.4 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.98A>C (p.H33P)

Variant1ClinVarID: N/A

Variant1CAID: CA355945475

Variant2: c.1402+2T>G

Variant2ClinVarID: 553131

Variant2CAID: CA355964392

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 21, female, Han origin, 10 years old (age at diagnosis)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001387, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly, Mongolian macula (HP:0001263, HP:0000256, HP:0011369)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 0.2 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1898C>T (p.S633L)

Variant1ClinVarID: 556406

Variant1CAID: CA355966010

Variant2: c.536C>G (p.T179R)

Variant2ClinVarID: 556358

Variant2CAID: CA355961718

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 36, female, Han origin, 5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Macrocephaly, Joint stiffness, Hepatosplenomegaly, Airway obstruction (HP:0000256, HP:0001387, HP:0001433, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Mongolian macula, Hernia, (HP:0001263, HP:0011369, HP:0100790)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.159C>A (p.C53X)

Variant1ClinVarID: 1458768

Variant1CAID: N/A

Variant2: c.1037T>G (p.L346R)

Variant2ClinVarID: 11927

Variant2CAID: CA256128

AdditionalVariants: N/A

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 54, male, Han origin, age of diagnosis not available

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: IDUA activity 0.6 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.236C>T (p.A79V)

Variant1ClinVarID: 1458769

Variant1CAID: CA356987

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 43, male, Han origin, 5 years old (age at diagnosis)

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: Joint stiffness, Mongolian macula, Hepatosplenomegaly, Hernia, Airway obstruction (HP:0001387, HP:0011369, HP:0001433, HP:0100790, HP:0006536)

CaseHPOFreeText: N/A

CaseNotHPOs: Global Developmental Delay, Macrocephaly (HP:0001263, HP:0000256)

CaseNotHPOFreeText: Cardiac disease

CaseEnzymeAssay: IDUA activity 1.5 nmol/h/mg protein. The normal range in Chinese controls was found to be 27.2–52 nmol/h/mg protein.

CaseUrineGAGs: Diagnosis was confirmed biochemically by the demonstration of an increased excretion of urinary dermatan sulfate and heparan sulfate.

CaseERT: N/A

CaseBMT: N/A

Variant1: c.300-3C>G

Variant1ClinVarID: 551563

Variant1CAID: CA549265042

Variant2: c.530dupT (p.Glu178ArgfsTer5) (Paper refers to the variant as c.531dupT, there is a typo in the article where all duplication variants are one base pair off)

Variant2ClinVarID: N/A

Variant2CAID: CA2586973520

AdditionalVariants: c.1037T>G (p.L346R)

ParentalGenotype: The transmission of sequence variations found in each patient was inferred by sequencing the corresponding exons of the patient's parents - confirmed in trans by parental testing.

PreviouslyPublished N/A

Case#: Patient 10, born in 2010 (paper published in 2017), 6 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 60 ng/mol (26 weight matched enzyme reference assay)

CaseUrineGAGs: 0.29 DS/CS

CaseERT: Yes

CaseBMT: Yes, Cord

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 14, born in 1998 (paper published in 2017), 19 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding, cataract (HP:0007957, HP:0000518)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy (HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 31.4 ng/mol (60.7 weight matched enzyme reference assay)

CaseUrineGAGs: 0.60 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.979G>C (p.A327P)

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 24, born in 2009 (paper published in 2017), 8 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Cataract, retinopathy (HP:0000518, HP:0000488)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 48.88 ng/mol (48.75 weight matched enzyme reference assay)

CaseUrineGAGs: 0.28 DS/CS

CaseERT: Yes

CaseBMT: Yes, MUD

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 7, born in 2005 (paper published in 2017), 16 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 62.57 ng/mol (34.3 weight matched enzyme reference assay)

CaseUrineGAGs: 0.59 DS/CS

CaseERT: No

CaseBMT: Yes, Cord

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.386-2A>G

Variant2ClinVarID: 222994

Variant2CAID: CA356991

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, born in 2000 (paper published in 2017), 18 months (age at first treatment)

DiseaseAssertion: MPSI-H

FamilyInfo: N/A

CasePresentingHPOs: Corneal clouding (HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: Retinopathy, cataract (HP:0000488, HP:0000518)

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 28 ng/mol (38 weight matched enzyme reference assay)

CaseUrineGAGs: 0.36 DS/CS

CaseERT: No

CaseBMT: Yes, MUD

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.979G>C (p.A327P)

Variant2ClinVarID: 167190

Variant2CAID: CA234128

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 109, Far East district of the Russian Federation

DiseaseAssertion: MPS1, Severe

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: IdA activity in DBS=0,01 leukocytes, severe phenotype, hyperexcretion of urine heparan and dermatan sulfate

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Electrophoresis of urine GAGs and measurement of lysosomal enzyme activity in peripheral blood leukocytes or DBSs were performed for all patients with suspected MPS I

GenotypingMethod: The 14 exons and exon–intron boundaries of the IDUA gene were amplified from DNA samples. Sanger sequencing of each one of the 14 exons was performed. PCR products containing mutations were re-sequenced in both directions. The mutations were further confirmed where possible by restriction analysis (data not shown).

PreviouslyPublished:

Variant: NM_000203.5:c.[208C>T];[1029C>A]

ClinVar: 222997

CAID: CA356984

SupplementalData: n/a

Case#: Patient 108, Central district of the Russian Federation

DiseaseAssertion: MPS1, Severe

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: IdA activity in DBS=0,01 DBS, severe phenotype, hyperexcretion of urine heparan and dermatan sulfate

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Electrophoresis of urine GAGs and measurement of lysosomal enzyme activity in peripheral blood leukocytes or DBSs were performed for all patients with suspected MPS I

GenotypingMethod: The 14 exons and exon–intron boundaries of the IDUA gene were amplified from DNA samples. Sanger sequencing of each one of the 14 exons was performed. PCR products containing mutations were re-sequenced in both directions. The mutations were further confirmed where possible by restriction analysis (data not shown).

PreviouslyPublished:

Variant: NM_000203.5:c.[208C>T];[1029C>A]

ClinVar: 222997

CAID: CA356984

SupplementalData: n/a

Case#: Infant 3

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.18 nmol/h/mg; normal range, 6-71.4 nmol/h/mg

CaseUrineGAGs: 25.49 mg/mmol creatinine; normal ranges, 0-53 mg/mmol creatinine

CaseERT: N/A

CaseBMT: N/A

Variant1: c.900G>A (p.A300=) homozygous for this variant + homozygous with a 2nd variant

Variant1ClinVarID: 1107522

Variant1CAID: CA438057521

Variant2: c.904C>A (p.P302T) homozygous for this variant + the first variant

Variant2ClinVarID: 1067236

Variant2CAID: CA355962529

AdditionalVariants: N/A

ParentalGenotype: c.900G>A (homozygous); c.904C>A (homozygous)

PreviouslyPublished N/A

PMID: 28728811

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 87, Turkey

DiseaseAssertion: MPS1-H

FamilyInfo: Consanguineous parents

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.956_972+9delinsTA

Variant1ClinVarID: N/A

Variant1CAID: CA3271845954

Variant2: c.956_972+9delinsTA

Variant2ClinVarID: N/A

Variant2CAID: CA3271845954

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 59, Poland

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.656G>A (p.G219E)

Variant1ClinVarID: 4078973

Variant1CAID: CA355962006

Variant2: c.917G>T (p.W306L)

Variant2ClinVarID: 2203497

Variant2CAID: CA355962596

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 29, Italy

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: c.878_889dup

Variant2ClinVarID: 550382

Variant2CAID: CA2802114

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, Italy

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1189+5G>A

Variant1ClinVarID: 551848

Variant1CAID: CA658823290

Variant2: c.46_57del

Variant2ClinVarID: 92643

Variant2CAID: CA220509

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished Yes - PMID: 23210910

Case#: Patient 35, Italy

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.398_403del (p.Met133_Gly134del)

Variant2ClinVarID: 863830

Variant2CAID: CA2801912

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 49, Poland

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.878_889dup (p.Thr293_Tyr296dup)

Variant1ClinVarID: 550382

Variant1CAID: CA2802114

Variant2: c.1181_1189dup (p.Ala394_Leu396dup)

Variant2ClinVarID: 3720561

Variant2CAID: CA549264540

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 32, Italy

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1225G>A (p.G265R)

Variant2ClinVarID: 1084956

Variant2CAID: CA91169920

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 82, Turkey

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1469T>C (p.L490P)

Variant1ClinVarID: 11919

Variant1CAID: CA220503

Variant2: c.1469T>C (p.L490P)

Variant2ClinVarID: 11919

Variant2CAID: CA220503

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10, Italy

DiseaseAssertion: MPS1-H/S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.1603C>T (p.L535F)

Variant2ClinVarID: 638076

Variant2CAID: CA355865038

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 65, Spain

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.979G>C (p.A327P)

Variant1ClinVarID: 167190

Variant1CAID: CA234128

Variant2: c.1154C>G (p.P385R)

Variant2ClinVarID: 556024

Variant2CAID: CA355963438

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 22 (see Table 2), 37 weeks (Gestational age)

DiseaseAssertion: MPS1-H/S

FamilyInfo: Homozygous twin of Patient 23 (see Table 2)

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1598C>G (p.P533R)

Variant1ClinVarID: 11910

Variant1CAID: CA256112

Variant2: c.1598C>G (p.P533R)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10 (see Table 2), Gestational age not available

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1205G>A (p.W402X)

Variant1ClinVarID: 11908

Variant1CAID: CA220498

Variant2: c.653T>C (p.L218P)

Variant2ClinVarID: 222995

Variant2CAID: CA:356986

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 30 (see Table 2), 40 weeks (Gestational age)

DiseaseAssertion: MPS1-S

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: Inguinal hernia (HP:0000023)

CaseNotHPOFreeText: Upper respiratory tract involvement

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.474-2A>G (new nomenclature: c.386-2A>G)

Variant1ClinVarID: 222994

Variant1CAID: CA356991

Variant2: c.1148G>A (p.R383H)

Variant2ClinVarID: 558189

Variant2CAID: CA:2802205

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 14 (see Table 2), 41 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: Upper respiratory tract involvement

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1100C>A (p.A367E)

Variant1ClinVarID: 3769492

Variant1CAID: CA355963330

Variant2: c.1650del117 (c.1650_1766del)

Variant2ClinVarID: N/A

Variant2CAID: CA3250142363

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 15 (see Table 2), 38 weeks, 1 day (Gestational age)

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Inguinal hernia (HP:0000023)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 0.23 nmol x mg-1 × hr-1

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.494-1G > A

Variant1ClinVarID: 557942

Variant1CAID: CA355961634

Variant2: c.494-1G > A

Variant2ClinVarID: 557942

Variant2CAID: CA355961634

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: R383H

Variant1ClinVarID: 558189

Variant1CAID: CA2802205

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: R628P

Variant1ClinVarID: 1064675

Variant1CAID: CA2802464

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: R619G

Variant1ClinVarID: 11924

Variant1CAID: CA256125

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: A361T

Variant1ClinVarID: 92624

Variant1CAID: CA145865

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: Q380R

Variant1ClinVarID: 550799

Variant1CAID: CA2802202

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: G219E

Variant1ClinVarID:

Variant1CAID: CA355962006

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: D349N

Variant1ClinVarID: 92623

Variant1CAID: CA220497

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: H82Q

Variant1ClinVarID:

Variant1CAID: CA355946477

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Variant not associated with a proband. Variant listed in supplementary materials in Supplementary Table 4

DiseaseAssertion: Mucopolysaccharidosis type I, MPS I

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: M133I

Variant1ClinVarID:

Variant1CAID: CA91166179

Variant2: N/A

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient No. 4 (Table 1), White race, male, 1.21 years old (age at time of gene therapy), 95 IQ score, 2.07 years since gene therapy (2 years since latest visit)

DiseaseAssertion: MPS-IH

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.208C>T (p.Q70X)

Variant1ClinVarID: 11909

Variant1CAID: CA204563

Variant2: c.208C>T (p.Q70X)

Variant2ClinVarID: 11909

Variant2CAID: CA204563

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient No. 2 (Table 1), Arabic Druze ethnic group, male, 1.15 years old (age at time of gene therapy), 100 IQ score, 2.40 years since gene therapy, 2 years since latest visit

DiseaseAssertion: MPS-IH

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.192C>A (p.Y64X)

Variant1ClinVarID: 11914

Variant1CAID: CA256113

Variant2: c.192C>A (p.Y64X)

Variant2ClinVarID: 11914

Variant2CAID: CA256113

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient No. 7 (Table 1), Black race, male, 1.71 years (age at time of gene therapy), 80 IQ score, 1.73 years since gene therapy (1.5 years since latest visit)

DiseaseAssertion: MPS-IH

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: N/A

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: Yes

Variant1: c.923_926delTGCC (p.L308HfsX8)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.923_926delTGCC (p.L308HfsX8)

Variant2ClinVarID: N/A

Variant2CAID: N/A

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

PMID: 34788506

Gene: IDUA

Disease: MPS1

Inheritance: Autosomal recessive

Case#: Patient 52, 2 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections (HP:0000280, HP:0001433, HP:0007957, HP:0002719)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.395C>T (p.Leu132Pro) in the article - incorrect variant. Possible correct nomenclature is c.395T>C (p.Leu132Pro) or c.394C>T (p.Leu132=)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.1839delT (p.Val614Serfs*7)

Variant2ClinVarID: N/A

Variant2CAID: CA2586965995

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 59, 8 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of Patient 58

CasePresentingHPOs: Coarse facial features, corneal clouding, dysostosis multiplex (HP:0000280, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.8% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1044C>G (p.Asn348Lys)

Variant1ClinVarID: 557870

Variant1CAID: CA2802172

Variant2: c.1598C>G (p.Pro533Arg)

Variant2ClinVarID: 11910

Variant2CAID: CA256112

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 2, 5 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, corneal clouding, recurrent infections, intellectual disability (HP:0000280, HP:0007957, HP:0002719, HP:0001249)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.203G>A (p.Trp68Ter)

Variant1ClinVarID: 2734634

Variant1CAID: CA2801137

Variant2: c.203G>A (p.Trp68Ter)

Variant2ClinVarID: 2734634

Variant2CAID: CA2801137

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 61, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, intellectual disability (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0001249)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.5% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1195_1197del (p.Glu399del)

Variant1ClinVarID: 2498386

Variant1CAID: CA549264677

Variant2: c.1249_1275del (p.Thr417_His425fs*55)

Variant2ClinVarID: 556156

Variant2CAID: CA658823291

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 13, 9 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding (HP:0000280, HP:0001433, HP:0002828, HP:0007957)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.532G>A (p.Glu178Lys)

Variant1ClinVarID: 2203495

Variant1CAID: CA355961709

Variant2: c.532G>A (p.Glu178Lys)

Variant2ClinVarID: 2203495

Variant2CAID: CA355961709

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 8, 3 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, hernia (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.1% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.436A>T (p.Lys146Ter)

Variant1ClinVarID: N/A

Variant1CAID: CA355961453

Variant2: c.436A>T (p.Lys146Ter)

Variant2ClinVarID: N/A

Variant2CAID: CA355961453

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 27, 4 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, dysostosis multiplex (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1249_1275del (p.Thr417_His425del)

Variant1ClinVarID: 556156

Variant1CAID: CA658823291

Variant2: c.1249_1275del (p.Thr417_His425del)

Variant2ClinVarID: 556156

Variant2CAID: CA658823291

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 42, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex (HP:0000280, HP:0002828, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 3.1% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1855C>T (p.Arg619Ter)

Variant1ClinVarID: 280976

Variant1CAID: CA2802455

Variant2: c.1855C>T (p.Arg619Ter)

Variant2ClinVarID: 280976

Variant2CAID: CA2802455

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 37, 1 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, joint contractures, corneal clouding, dysostosis multiplex (HP:0000280, HP:0002828, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 4.8% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 28, 8 months old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, dysostosis multiplex (HP:0000280, HP:0001433, HP:0007957, HP:0000943)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1273delC (p.His425Thrfs*15)

Variant1ClinVarID: 3391381

Variant1CAID: CA2586965976

Variant2: c.1273delC (p.His425Thrfs*15)

Variant2ClinVarID: 556156

Variant2CAID: CA2586965976

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 50, 2 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, corneal clouding, recurrent infections, hernia (HP:0000280, HP:0001433, HP:0007957, HP:0002719, HP:0100790)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.2% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.238G>T (p.Val80Phe)

Variant1ClinVarID: N/A

Variant1CAID: CA355946451

Variant2: c.784delC (p.His262Thrfs*55)

Variant2ClinVarID: 956890

Variant2CAID: CA2802083

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 10, 1 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: Sibling of patient 11

CasePresentingHPOs: Coarse facial features, recurrent infections, dysostosis multiplex, intellectual disability, hernia (HP:0000280, HP:0002719, HP:0000943, HP:0001249, HP:0100790)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.531C>G (p.Phe177Leu)

Variant1ClinVarID: 2432729

Variant1CAID: CA2801983

Variant2: c.531C>G (p.Phe177Leu)

Variant2ClinVarID: 2432729

Variant2CAID: CA2801983

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 30, 8 years old (age at report), male, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, corneal clouding, recurrent infections, dysostosis multiplex, intellectual disability (HP:0000280, HP:0001433, HP:0002828, HP:0007957, HP:0002719, HP:0000943, HP:0001249)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.7% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.1373T>C (p.Leu458Pro)

Variant1ClinVarID: N/A

Variant1CAID: CA355964255

Variant2: c.1373T>C (p.Leu458Pro)

Variant2ClinVarID: N/A

Variant2CAID: CA355964255

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A

Case#: Patient 51, 2 years old (age at report), female, Indian

DiseaseAssertion: MPS1-H

FamilyInfo: N/A

CasePresentingHPOs: Coarse facial features, hepatosplenomegaly, joint contractures, dysostosis multiplex (HP:0000280, HP:0001433, HP:0002828, HP:0000943)

CaseHPOFreeText: Cardiac disease

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CaseEnzymeAssay: 2.4% (Range of residual enzyme activity: 0.0%-4.8%)

CaseUrineGAGs: N/A

CaseERT: N/A

CaseBMT: N/A

Variant1: c.265G>C in the article - incorrect variant but unknown what the correct nomenclature is. Could be c.265C>G (p.Arg89Gly) or c.266G>C (p.Arg89Pro)

Variant1ClinVarID: N/A

Variant1CAID: N/A

Variant2: c.779C>T (p.Ser260Phe)

Variant2ClinVarID: 3895951

Variant2CAID: CA355962251

AdditionalVariants: N/A

ParentalGenotype: N/A

PreviouslyPublished N/A