title: Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.
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.
authors.affiliation: 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.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Akahori
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, MD, United States of America.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Sergeev
authors.affiliation: Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yoshitake
authors.affiliation: Laboratory of DNA Data Analysis, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Life Science Accelerator Technology Group, Transcriptome Technology Team, Yokohama, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Furuno
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Japan.
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Laboratory of Visual Physiology, National Institute of Sensory Organs, Tokyo, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Tsunoda
authors.affiliation: Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Shinoda
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kuniyoshi
authors.affiliation: Department of Human Genetics, Yokohama City University, Yokohama, Japan.
authors.forename: Yohinori
authors.initials: Y
authors.lastname: Tsurusaki
authors.affiliation: Department of Human Genetics, Yokohama City University, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001483:Base Sequence; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics*; D059472:Exome; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005808:Genes, Recessive; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D059645:Mutation Rate; D010375:Pedigree; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
chemical_list: C518243:CNGA1 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; C533105:EYS protein, human; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; C550125:PCARE protein, human; C105443:TULP1 protein, human; C112735:USH2A protein, human; C104998:1-stearoyl-2-arachidonoylglycerol kinase; D017853:Phosphotransferases (Alcohol Group Acceptor)