Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa

Satoshi Katagiri; Masakazu Akahori; Yuri Sergeev; Kazutoshi Yoshitake; Kazuho Ikeo; Masaaki Furuno; Takaaki Hayashi; Mineo Kondo; Shinji Ueno; Kazushige Tsunoda; Kei Shinoda; Kazuki Kuniyoshi; Yohinori Tsurusaki; Naomichi Matsumoto; Hiroshi Tsuneoka; Takeshi Iwata

doi:10.1371/journal.pone.0108721

Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa

PLoS One. 2014 Sep 30;9(9):e108721. doi: 10.1371/journal.pone.0108721. eCollection 2014.

Authors

Satoshi Katagiri¹, Masakazu Akahori², Yuri Sergeev³, Kazutoshi Yoshitake⁴, Kazuho Ikeo⁴, Masaaki Furuno⁵, Takaaki Hayashi⁶, Mineo Kondo⁷, Shinji Ueno⁸, Kazushige Tsunoda⁹, Kei Shinoda¹⁰, Kazuki Kuniyoshi¹¹, Yohinori Tsurusaki¹², Naomichi Matsumoto¹², Hiroshi Tsuneoka⁶, Takeshi Iwata²

Affiliations

¹ Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan; Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
² Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
³ National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
⁴ Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, Japan.
⁵ RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Life Science Accelerator Technology Group, Transcriptome Technology Team, Yokohama, Japan.
⁶ Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
⁷ Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan.
⁸ Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁹ Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan.
¹⁰ Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan.
¹¹ Department of Ophthalmology, Kinki University Faculty of Medicine, Osaka, Japan.
¹² Department of Human Genetics, Yokohama City University, Yokohama, Japan.

Abstract

Objective: The purpose of this study was to investigate frequent disease-causing gene mutations in autosomal recessive retinitis pigmentosa (arRP) in the Japanese population.

Methods: In total, 99 Japanese patients with non-syndromic and unrelated arRP or sporadic RP (spRP) were recruited in this study and ophthalmic examinations were conducted for the diagnosis of RP. Among these patients, whole exome sequencing analysis of 30 RP patients and direct sequencing screening of all CNGA1 exons of the other 69 RP patients were performed.

Results: Whole exome sequencing of 30 arRP/spRP patients identified disease-causing gene mutations of CNGA1 (four patients), EYS (three patients) and SAG (one patient) in eight patients and potential disease-causing gene variants of USH2A (two patients), EYS (one patient), TULP1 (one patient) and C2orf71 (one patient) in five patients. Screening of an additional 69 arRP/spRP patients for the CNGA1 gene mutation revealed one patient with a homozygous mutation.

Conclusions: This is the first identification of CNGA1 mutations in arRP Japanese patients. The frequency of CNGA1 gene mutation was 5.1% (5/99 patients). CNGA1 mutations are one of the most frequent arRP-causing mutations in Japanese patients.

Publication types

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

MeSH terms

Adult
Aged
Asian People
Base Sequence
Cyclic Nucleotide-Gated Cation Channels / genetics*
Exome*
Exons
Extracellular Matrix Proteins / genetics
Eye Proteins / genetics
Female
Genes, Recessive
High-Throughput Nucleotide Sequencing
Homozygote
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation Rate*
Pedigree
Phosphotransferases (Alcohol Group Acceptor) / genetics
Retinitis Pigmentosa / ethnology
Retinitis Pigmentosa / genetics*
Retinitis Pigmentosa / pathology

Substances

CNGA1 protein, human
Cyclic Nucleotide-Gated Cation Channels
EYS protein, human
Extracellular Matrix Proteins
Eye Proteins
PCARE protein, human
TULP1 protein, human
USH2A protein, human
1-stearoyl-2-arachidonoylglycerol kinase
Phosphotransferases (Alcohol Group Acceptor)

Grants and funding

This study was supported by the grants to T.I. from the Ministry of Health, Labor, and Welfare of Japan (13803661); to M.A. and T.H. from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Grant-in-Aid for Scientific Research C, 25462744 and 25462738); to T.H. from the Vehicle Racing Commemorative Foundation; and to M.F. from the Research Grant for RIKEN Omics Science Center MEXT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.