Single-Exome sequencing identified a novel RP2 mutation in a child with X-linked retinitis pigmentosa

• Published in: Canadian journal of ophthalmology 2016-10, Vol.51 (5), p.326-330
• Main Authors: Lim, Hassol, BS, MD, PhD, Park, Young-Mi, MS, Lee, Jong-Keuk, PhD, Taek Lim, Hyun, MD, PhD
• Format: Article
• Language: English
• Subjects: Asian Continental Ancestry Group - genetics; Child; Codon, Nonsense - genetics; DNA Mutational Analysis; Electroretinography; Exome - genetics; Eye Proteins - genetics; Frameshift Mutation; Genetic Diseases, X-Linked - diagnostic imaging; Genetic Diseases, X-Linked - genetics; Humans; Internal Medicine; Intracellular Signaling Peptides and Proteins - genetics; Male; Membrane Proteins - genetics; Ophthalmology; Pedigree; Republic of Korea; Retinitis Pigmentosa - diagnostic imaging; Retinitis Pigmentosa - genetics; Sequence Analysis, DNA; Tomography, Optical Coherence
• ISSN: 0008-4182; 1715-3360
• DOI: 10.1016/j.jcjo.2016.03.017

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. Design Exome sequencing study based on clinical examination data. Participants 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.