Exome sequencing analysis identifies novel homozygous mutation in ABCA4 in a Chinese family with Stargardt disease

作     者：Xiao-Dan Hao Ying Liu Bao-Wei Li Wei Wu Xiao-Wen Zhao 

作者机构：Institute for Translational MedicineCollege of MedicineQingdao UniversityQingdao 266021Shandong ProvinceChina State Key Laboratory Cultivation BaseShandong Provincial Key Laboratory of OphthalmologyShandong Eye InstituteShandong First Medical University&Shandong Academy of Medical SciencesQingdao 266071Shandong ProvinceChina 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志（英文版）)

年 卷 期：2020年第13卷第4期

页      面：671-676页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：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) 

主　　题：Stargardt disease whole-exome sequencing ABCA4 novel mutation retina 

摘      要：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 ***: 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 Prot Param 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 ***: Using WES, a novel homozygous mutation(NM_000350: c.G3190 C, p.G1064 R) 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.G1064 R 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.G3190 C of ABCA4) of STGD. This extends the existing spectrum of disease-causing mutations and further defines the genotype-phenotype correlations.