Original Research ARTICLE
ABCA4 gene screening in a Chinese cohort with Stargardt disease: Identification of 37 novel variants
- 1Eye & ENT Hospital, Fudan University, China
- 2Beijing Genomics Institute (BGI), China
- 3City University of Hong Kong, Hong Kong
Purpose: To clarify the mutation spectrum and frequency of ABCA4 in a Chinese cohort with Stargardt disease (STGD1).
Methods: A total of 153 subjects, comprising 25 families (25 probands and their family members) and 71 sporadic cases, were recruited for the analysis of ABCA4 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.
Results: The total variant detection rate of at least one ABCA4 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 de novo 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.
Conclusion: Thirty-seven novel variants are detected using panel-based NGS, including one de novo variant, further extending the mutation spectrum of ABCA4. The common variants in a population from eastern China with STGD1 are also identified.
Keywords: STGD1, Next-generation sequencing, ABCA4 gene, Mutation spectrum, variant frequency
Received: 27 Apr 2019;
Accepted: 22 Jul 2019.
Copyright: © 2019 Hu, Li, Gao, Qi, Xu, Zhang, Wang, Wang, Chang, Li, Wang, Chen, Zhang, Xu and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
PhD. Shenghai Zhang, Eye & ENT Hospital, Fudan University, Shanghai, 200032, Shanghai Municipality, China, email@example.com
PhD. Gezhi Xu, Eye & ENT Hospital, Fudan University, Shanghai, 200032, Shanghai Municipality, China, firstname.lastname@example.org
PhD. Jihong Wu, Eye & ENT Hospital, Fudan University, Shanghai, 200032, Shanghai Municipality, China, email@example.com