title: Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular Atrophy, Cataracts, and High Myopia.
abstract: OBJECTIVE
  More than 50 genes are reported as causative genes of autosomal recessive (ar) retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). It is challenging to identify causative mutations for arRP and arCRD. The purpose of the present study was to investigate clinical and genetic features of two siblings with early-onset retinal dystrophy.
  
  
  METHODS
  Whole-exome sequencing was conducted for the two affected siblings and their unaffected brother and mother from a Japanese family. We performed complete ophthalmic examinations, including visual acuity, funduscopy, visual-field testing, electroretinography and optical coherence tomography.
  
  
  RESULTS
  Whole-exome sequencing analysis identified novel compound heterozygous mutations, a splice site mutation (c.374 + 2T > C in intron 4) and a deletion mutation (c.575delC [p.T192MfsX28] in exon 6) of chromosome 8 open reading frame 37 (C8orf37) gene, which encodes a ciliary protein, in both patients. The mother carried the truncating mutation, and the brother carried neither mutation. Ophthalmic examinations revealed diffuse retinal degeneration, macular atrophy, non-recordable electroretinography responses, cataracts, and high myopia in both patients, who could not be diagnosed with either RP or CRD because of the severe retinal degeneration and early onset disease. Longitudinal follow-up of the patients revealed highly progressive retinal degeneration, macular atrophy, and visual field loss.
  
  
  CONCLUSIONS
  Recessive C8orf37 mutations have been identified in early to adolescent-onset arRP and arCRD with macular involvement. Our study identified two novel truncating mutations of the C8orf37 gene in siblings with early-onset retinal dystrophy, macular atrophy, cataracts, and high myopia.
authors.affiliation: a Division of Molecular and Cellular Biology , National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center , Tokyo , Japan .|b Department of Ophthalmology , The Jikei University School of Medicine , Tokyo , Japan , and.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katagiri
authors.affiliation: b Department of Ophthalmology , The Jikei University School of Medicine , Tokyo , Japan , and.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: c Laboratory of DNA Data Analysis, National Institute of Genetics , Shizuoka , Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Yoshitake
authors.affiliation: a 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: c Laboratory of DNA Data Analysis, National Institute of Genetics , Shizuoka , Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.affiliation: b Department of Ophthalmology , The Jikei University School of Medicine , Tokyo , Japan , and.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Gekka
authors.affiliation: b Department of Ophthalmology , The Jikei University School of Medicine , Tokyo , Japan , and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tsuneoka
authors.affiliation: a 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; D001483:Base Sequence; D002386:Cataract / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D005260:Female; D005451:Fluorescein Angiography; D057092:Geographic Atrophy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D047728:Myopia, Degenerative / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D058499:Retinal Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D035781:Siblings; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D011506:Proteins; C570604:CFAP418 protein, human
keywords: C8orf37; early-onset retinal dystrophy; mutation; whole-exome sequencing