Exome sequencing analysis identifies compound heterozygous mutation in ABCA4 in a Chinese family with Stargardt disease

Yu Zhou; Siyu Tao; Hui Chen; Lulin Huang; Xiong Zhu; Youping Li; Zhili Wang; He Lin; Fang Hao; Zhenglin Yang; Liya Wang; Xianjun Zhu

doi:10.1371/journal.pone.0091962

Exome sequencing analysis identifies compound heterozygous mutation in ABCA4 in a Chinese family with Stargardt disease

PLoS One. 2014 Mar 14;9(3):e91962. doi: 10.1371/journal.pone.0091962. eCollection 2014.

Authors

Yu Zhou¹, Siyu Tao², Hui Chen³, Lulin Huang¹, Xiong Zhu¹, Youping Li⁴, Zhili Wang², He Lin⁴, Fang Hao⁴, Zhenglin Yang⁵, Liya Wang², Xianjun Zhu⁶

Affiliations

¹ 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.
² Henan Eye Hospital and Henan Eye Institute, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China; Laboratory Animal Institute, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
⁴ 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.
⁵ 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; Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁶ 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; Key Laboratory for NeuroInformation of Ministry of Education, University of Electronic Science and Technology of China, Chengdu, Sichuan, China; College of Life Sciences and Engineering, Xinan Jiaotong University, Chengdu, Sichuan, China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP-Binding Cassette Transporters / genetics*
Adolescent
Adult
Amino Acid Sequence
Animals
Asian People / genetics*
Base Sequence
DNA Mutational Analysis*
Exome / genetics*
Female
Genomics
Heterozygote*
Humans
Macular Degeneration / genetics
Male
Molecular Sequence Data
Pedigree*
Polymorphism, Genetic
Stargardt Disease
Young Adult

Substances

ABCA4 protein, human
ATP-Binding Cassette Transporters

Grants and funding

This research was supported by the National Natural Science Foundation of China [81025006, 81170883 (Z.Y.), 81271007 (X.Z.)], and Department of Science and Technology of Sichuan Province, China (SZ20120209, Z.Y.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.