Case#: STGD102, 10-14yo at onset, German

DiseaseAssertion: STGD

FamilyInfo: segregation in family

CasePresentingHPOs:

CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

PreviouslyPublished: n/a

Variant: R572Q-2588G→C IVS35+2T→A in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7900

CAID: CA226918

SupplementalData: n/a

Case#: Patient #15, Moorfields Eye Hospital, London, UK, female, 39yo at onset, 51yo at report,

DiseaseAssertion: ABCA4-Associated Retinopathy, clinical diagnosis of STG

FamilyInfo: no additional family-member WGS data available

CasePresentingHPOs:

CaseHPOFreeText: BCVA= OD: 6/9, OS: 6/9, Fishmann Classification=2 (fleck-like lesions anterior to the vascular arcades and/or nasal to the optic disc), early changes to foveal photoreceptors, Extent of FAF abnormalities with Regard to Vascular Arcades: beyond. ffERG Group: 1(normal). PERG: Abnormal. FAF in Fig. 1B. characteristic yellow-white pisciform flecks in the RPE of the posterior pole that were hyperautofluorescent on FAF imaging or progressive atrophy of the macular RPE

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCA4 mutation screening was performed by next-generation sequencing, sequenced as part of the retinal panel at the Molecular Vision Lab

PreviouslyPublished:

Variant: c.5196+1137G>A p.[=,M1733Efs∗78] c.[1715G>A;2588G>C] p.[(R572Q;G863A,G863del]

ClinVar: 7900

CAID: CA226918

SupplementalData:

Case#: Patient #32, male, 60yo at baseline visit, "late" age of onset

DiseaseAssertion: ABCA4-related retinopathy with secondary RPE atrophy

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: Inclusion criteria were defined as 1) presence of at least one mutated allele in ABCA4 (NM_000350.2) in Sanger sequencing with multiplex ligation-dependent probe amplification analysis or next-generation sequencing 2) a compatible phenotype with flecks at the level of the RPE consistent with ABCA4 -related Stargardt disease 3) presence of RPE atrophy, and 4) serial examinations with an interval of at least 6 months. RPE atrophy to the end-stage (i.e., demarcated lesions with ≥90% darkness of the optic disc under short-wavelength excitation light, DDAF) that previously showed highest interreader agreement.7 The size of DDAF has to be at least 0.05 mm 2 (each single atrophic area in cases of multifocality), and the entire lesion must be completely visualized on the AF image at each visit to be advanced for analysis. Self-reported symptom onset into early-onset (≤10 years), intermediate-onset (11–44 years), and late-onset (≥45 years). ff-ERG based Category: Group 1 contained eyes with normal scotopic and photopic responses; Group 2, eyes with normal scotopic responses, but reduced (over 2 SDs) photopic B-wave and 30-Hz flicker amplitudes; and Group 3, eyes with impairment of both rod- and cone-driven responses. BCVA: OD=0, OS=0 [LogMAR] .

CaseNotHPOs:

CaseNotHPOFreeText: Insufficient pupil dilation, additional retinal pathology, previous retinal treatment, or other ocular comorbidities substantially affecting image quality led to exclusion from the study

GenotypingMethod: Sanger sequencing with multiplex ligation-dependent probe amplification analysis or next-generation sequencing

PreviouslyPublished: n/a

Variant: allele 1: c.52C>T/p.(Arg18Trp) // c.1715G>A/p.(Arg572Gln) // c.2828G>A/p.(Arg943Gln) allele 2: c.1588G>A/p.(Gly863Ala) // c.5603A>T/p.(Asn1868Ile)

ClinVar: 7900

CAID: CA226918

SupplementalData: The supplemental table linked here contains genotype and phenotype information.