Zhou Yu, Tao Siyu, Chen Hui, Huang Lulin, Zhu Xiong, Li Youping, Wang Zhili, Lin He, Hao Fang, Yang Zhenglin, Wang Liya, Zhu Xianjun
Sichuan Provincial Key Laboratory for Human Disease Gene Study and Institute of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; Chengdu Institute of Biology, Chinese Academy of Sciences and Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China.
Henan Eye Hospital and Henan Eye Institute, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
PLoS One. 2014 Mar 14;9(3):e91962. doi: 10.1371/journal.pone.0091962. eCollection 2014.
Stargardt disease is the most common cause of juvenile macular dystrophy. Five subjects from a two-generation Chinese family with Stargardt disease are reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family initiated the disease during childhood, developing progressively impaired central vision and bilateral atrophic macular lesions in the retinal pigmental epithelium (RPE) that resembled a "beaten-bronze" appearance. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. Exome sequencing was used to analyze the exome of two patients II1, II2. A total of 50709 variations shared by the two patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in all family members by PCR and Sanger sequencing. Compound heterozygous variants p.Y808X and p.G607R of the ATP-binding cassette, sub-family A (ABC1), member 4 (ABCA4) gene, which encodes the ABCA4 protein, a member of the ATP-binding cassette (ABC) transport superfamily, were identified as causative mutations for Stargardt disease of this family. Our findings provide one novel ABCA4 mutation in Chinese patients with Stargardt disease.
斯塔加特病是青少年黄斑营养不良最常见的病因。本研究报告了一个患有斯塔加特病的中国两代家庭中的五名成员。所有家庭成员均接受了全面的眼科检查。该家庭的患者在儿童期发病，逐渐出现中心视力受损以及视网膜色素上皮（RPE）双侧萎缩性黄斑病变，呈现出“铜箔样”外观。采集了所有患者及其家庭成员的外周静脉血用于基因分析。外显子组测序用于分析两名患者II1、II2的外显子组。针对现有的变异数据库，对两名患者共有的50709个变异进行了多个筛选步骤。通过聚合酶链反应（PCR）和桑格测序在所有家庭成员中验证了鉴定出的变异。编码ATP结合盒转运超家族成员ABCA4蛋白的ATP结合盒A亚家族（ABC1）成员4（ABCA4）基因的复合杂合变异p.Y808X和p.G607R被确定为该家庭斯塔加特病的致病突变。我们的研究结果为中国斯塔加特病患者提供了一种新的ABCA4突变。
