ABCA4 Gene Screening in a Chinese Cohort With Stargardt Disease: Identification of 37 Novel Variants

<b>Purpose:</b> To clarify the mutation spectrum and frequency of <i>ABCA4</i> in a Chinese cohort with Stargardt disease (STGD1). <b>Methods:</b> A total of 153 subjects, comprising 25 families (25 probands and their family members) and 71 sporadic cases, were recruited for the analysis of <i>ABCA4</i> variants. All probands with STGD1 underwent a comprehensive ophthalmologic examination. Overall, 792 genes involved in common inherited eye diseases were screened for variants by panel-based next-generation sequencing (NGS). Variants were filtered and analyzed to evaluate possible pathogenicity. <b>Results:</b> The total variant detection rate of at least one <i>ABCA4</i> mutant allele was 84.3% (129/153): two or three disease-associated variants in 86 subjects (56.2%), one mutant allele in 43 subjects (28.1%), and no variants in 24 subjects (15.7%). Ninety-six variants were identified in the total cohort, which included 62 missense (64%), 15 splicing (16%), 11 frameshift (12%), 6 nonsense (6%), and 2 small insertion or deletion (2%) variants. Thirty-seven novel variants were found, including a <i>de novo</i> variant, c.4561delA. The most prevalent variant was c.101_106delCTTTAT (10.5%), followed by c.2894A > G (6.5%) and c.6563T > C (4.6%), in STGD1 patients from eastern China. <b>Conclusion:</b> Thirty-seven novel variants were detected using panel-based NGS, including one <i>de novo</i> variant, further extending the mutation spectrum of <i>ABCA4</i>. The common variants in a population from eastern China with STGD1 were also identified.