ABCA4 whole-gene sequencing, subsequent WGS, and segregation analysis identified a complex deep-intronic allele (NM_000350.2(ABCA4):c.[1555-5882C>A;1555-5784C>G]) in trans to the missense variant.
PMID: 39421326 (PMCID: PMC11675205)
Gene: ABCA4
HGNC ID: 34
Case#: Patient 24 (male)
DiseaseAssertion: STGD (Stargardt disease)
FamilyInfo: Caucasian family from Germany. Patient has two siblings carrying the variant but they are not clinically affected according to pedigree information.
CasePresentingHPOs: Decreased central visual acuity (HP:0000545) Macular atrophy (HP:0007754) Retinal flecks (HP:0030638) Abnormal fundus autofluorescence (HP:0030647) Macular degeneration (HP:0007754) Abnormal electroretinogram (HP:0000763)
CaseHPOFreeText: Male patient diagnosed before age 50 with Stargardt disease. Best corrected visual acuity (BCVA) approximately 0.05–0.2. Fundus imaging shows paracentral scotoma, macular atrophy, and hyperfluorescent flecks with sparing of the fovea. Autofluorescence demonstrates hyperreflective spots and patchy lesions with parafoveal involvement.
CaseNotHPOs: None explicitly reported.
CaseNotHPOFreeText: Pattern-like distribution of lesions noted on clinical examination.
Genotyping Method: Whole-exome sequencing (WES) with an in-house RD-associated gene panel including 619 candidate and disease-associated genes.
PreviouslyPublished: No (novel complex deep-intronic allele described in this study).
Variant: c.[1555-5882C>A;1555-5784C>G]
ClinVar: Not reported in ClinVar in the provided information.
CAID: CA272741; CA227172
SupplementalData: Segregation data and functional splicing analysis available in the supplemental data (Table S1, Figure S1) of the article.