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Yu-Chi Sung, Ding-Siang Huang, Chao-Wen Lin, Hsueh-Min Hsu, Chang-Hao Yang, Chung-May Yang, Fung-Rong Hu, Pei-Lung Chen, Ta-Ching Chen; The Genetic Characteristics of ABCA4-associated retinal degenerations in East Asia. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2389.
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© ARVO (1962-2015); The Authors (2016-present)
Mutation of ABCA4 gene may cause different types of retinal dystrophies, including Stargradt disease as well as retinitis pigmentosa. The ABCA4 protein is active following phototransduction to remove potentially toxic substances N-retinylidene-PE from photoreceptor cells. Here, we reported our experiences of genetic characteristics in ABCA4-associated retinal degenerations.
The reported cases were recruited in the TIP (Taiwan Inherited retinal diseases Project) program. All subjects received comprehensive ophthalmic examination in National Taiwan University Hospital. The blood sample was collected and the genomic DNA was sequenced by panel-based next-generation sequencing (NGS) with 215 genes associated with inherited retinal degenerations. NGS data were processed and pathogenicity of retained variants was predicted by algorithm analysis such as SIFT, PolyPhen-2, and database such as GnomAD. The criteria of classifying pathogenic variants were based on the ACMG standard and guideline.
In our first 370 probands recruited in TIP program, 34 families were identified having ABCA4 genetic defects as causative variants. Clinical phenotypes of these patients include Stargardt disease (58.8%), cone-rod dystrophy (8.8%) and retinitis pigmentosa (32.4%). Among them, we identified 37 different ABCA4 variants in our group, including 25 missense (67.5%), 3 nonsense (8.1%), 4 splicing (10.8%), 4 frameshift (10.8%) mutation, and 1 inframe deletion mutation (2.7%). Interestingly, the most prevalent variant, Arg602Trp, was found in 12 patients in our study, accounted significantly high incidence in our cohort (35.3%). Most Arg602Trp carriers were diagnosed with Stargardt disease (58.3%), remains 25% with retinitis pigmentosa, 16.7% with cone-rod dystrophy.
Here we report our experiences in genetic characteristics of ABCA4-associated retinal degenerations. In our cohorts, Arg602Trp had highest prevalence up to one third in our group. The variant is not so common in other previously published cohorts. Further study about Arg602Trp may be done to reveal possible founder effects and its pathogenic effects in retinal degenerations in the future.
This is a 2020 ARVO Annual Meeting abstract.
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