title: Single-Exome sequencing identified a novel RP2 mutation in a child with X-linked retinitis pigmentosa.
abstract: OBJECTIVE
  To present an efficient and successful application of a single-exome sequencing study in a family clinically diagnosed with X-linked retinitis pigmentosa.
  
  
  METHODS
  Exome sequencing study based on clinical examination data.
  
  
  METHODS
  An 8-year-old proband and his family.
  
  
  METHODS
  The proband and his family members underwent comprehensive ophthalmologic examinations. Exome sequencing was undertaken in the proband using Agilent SureSelect Human All Exon Kit and Illumina HiSeq 2000 platform. Bioinformatic analysis used Illumina pipeline with Burrows-Wheeler Aligner-Genome Analysis Toolkit (BWA-GATK), followed by ANNOVAR to perform variant functional annotation. All variants passing filter criteria were validated by Sanger sequencing to confirm familial segregation.
  
  
  RESULTS
  Analysis of exome sequence data identified a novel frameshift mutation in RP2 gene resulting in a premature stop codon (c.665delC, p.Pro222fsTer237). Sanger sequencing revealed this mutation co-segregated with the disease phenotype in the child's family.
  
  
  CONCLUSIONS
  We identified a novel causative mutation in RP2 from a single proband's exome sequence data analysis. This study highlights the effectiveness of the whole-exome sequencing in the genetic diagnosis of X-linked retinitis pigmentosa, over the conventional sequencing methods. Even using a single exome, exome sequencing technology would be able to pinpoint pathogenic variant(s) for X-linked retinitis pigmentosa, when properly applied with aid of adequate variant filtering strategy.
authors: Department of Life Science, Ewha Womans University, Seoul, Korea.
authors: Hassol
authors: H
authors: Lim
authors: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors: Young-Mi
authors: YM
authors: Park
authors: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea.
authors: Jong-Keuk
authors: JK
authors: Lee
authors: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, Korea; Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.. Electronic address: htlim@amc.seoul.kr.
authors: Hyun
authors: H
authors: Taek Lim
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D059472:Exome / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D016368:Frameshift Mutation; D019204:GTP-Binding Proteins; D040181:Genetic Diseases, X-Linked / Q000000981:diagnostic imaging / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010375:Pedigree; D056910:Republic of Korea; D012174:Retinitis Pigmentosa / Q000000981:diagnostic imaging / Q000235:genetics*; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C072178:RP2 protein, human; D019204:GTP-Binding Proteins