Abstract
Purpose :
Stargardt’s disease (STGD), as one of the most common inherited retinal degeneration, poses a significant threat to the juvenile vision. Most STGD patients have been identified with biallelic variants in ABCA4, while variants in other genes have also been reported to contribute to STGD-like macular dystrophies. This study aimed to investigate the genetic and clinical characteristics of STGD based on a large Chinese cohort.
Methods :
Rare variants in 11 gene associated with STGD were selected from exome sequencing data and further evaluated by multi-step bioinformatics. All the selected variants were defined according to ACMG/AMP criteria and confirmed by Sanger sequencing as well as co-segregation analysis. Clinical data of patient with pathogenic or likely pathogenic (P/LP) variants were detailly summarized, especially fundus performance.
Results :
Among our cohort of more than 300 patients diagnosed with STGD or inherited macular dystrophy, 63.0% families were confirmed with ABCA4-associated with STGD1 in autosomal recessive mode. The phenotypic heterogeneity of ABCA4 has been revealed to represent a sequential progression of a single disease. Ten patients from four unrelated families were confirmed with the heterozygous p.Arg373Cys in PROM1, which have been considered to cause STGD4. Unlike Stargardt disease alone, all patients with full-field fundus examination presented with macular dystrophy plus peripheral retinopathy mimicking retinitis pigmentosa. Patients with P/LP variants in BEST1 predominantly presented with vitelliform macular dystrophy, with no significant differences in clinical features between those with dominant or recessive traits, except for fundus performance. Truncations and missenses with more severe pathogenicity in PRPH2 primarily lead to RP, while only five probands exhibit macular degeneration similar to STGD. Additionally, there were no patients with STGD in our cohort were identified with P/LP variants in ELOVL4, TIMP3, PRDM13, RIMS1, IMPG1, IMPG2, and ALDH3A2, which have been reported to be associated with STGD.
Conclusions :
Based on our large cohort of Chinese patient pedigrees, we summarized the genetic spectrum of STGD patients in the Chinese population. Furthermore, we outlined the clinical phenotype characteristics of ABCA4, PROM1, BEST1, and PRPH2. This provides valuable assistance for future genetic counseling and diagnosis of STGD patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.