Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease
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Xiao-Dan Hao. Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, Shandong Province, China. haoxiaodan1987@163.com; Xiao-Wen Zhao. State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China. xiaowenzhao126@126.com

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Supported by the National Natural Science Foundation of China (No.81500763; No.81800805; No.81600721); Young and Middle-aged Scientists Research Awards Fund of Shandong Province (No.BS2015YY014); China Postdoctoral Science Foundation (No.2019M652311); Medical and Health Science and Technology Development Project of Shandong Province (No.2017WS012).

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    Abstract:

    AIM: To identify the disease-associated mutations in a Chinese Stargardt disease (STGD) family, extend the existing spectrum of disease-causing mutations and further define the genotype-phenotype correlations. METHODS: A Chinese STGD family and 200 normal controls were collected. Whole exome sequencing (WES) and bioinformatics analysis were performed to find the pathogenic gene mutation. Physico-chemical parameters of mutant and wildtype proteins were computed by ProtParam tool. Domains analysis was performed by SMART online software. HOPE online software was used to analyze the structural effects of mutation. Immunofluorescence, quantitative real-time polymerase chain reaction and Western blotting were used for expression analysis. RESULTS: Using WES, a novel homozygous mutation (NM_000350: c.G3190C, p.G1064R) in ABCA4 gene was identified. This mutation showed co-segregation with phenotype in this family. It was not found in the 200 unrelated health controls and absent from any databases. It was considered “Deleterious” as predicted by five function prediction softwares, and was highly conserved during evolution. ABCA4 was expressed highly in the human eye and mouse retina. The p.G1064R was located in AAA domain, may force the local backbone into an incorrect conformation, disturb the local structure, and reduce the activity of ATPase resulting in the disease pathology. CONCLUSION: We define a novel pathogenic mutation (c.G3190C of ABCA4) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations.

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Xiao-Dan Hao, Ying Liu, Bao-Wei Li, et al. Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease. Int J Ophthalmol, 2020,13(4):671-676

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Publication History
  • Received:May 22,2019
  • Revised:August 14,2019
  • Adopted:
  • Online: March 31,2020
  • Published: