AUTHOR=Hu Fang-Yuan , Li Jian-kang , Gao Feng-Juan , Qi Yu-He , Xu Ping , Zhang Yong-Jin , Wang Dan-Dan , Wang Lu-Sheng , Li Wei , Wang Min , Chen Fang , Shen Si-Mai , Xu Ge-Zhi , Zhang Sheng-Hai , Chang Qing , Wu Ji-Hong
TITLE=ABCA4 Gene Screening in a Chinese Cohort With Stargardt Disease: Identification of 37 Novel Variants
JOURNAL=Frontiers in Genetics
VOLUME=10
YEAR=2019
URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00773
DOI=10.3389/fgene.2019.00773
ISSN=1664-8021
ABSTRACT=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 were 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 were also identified.