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.

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.