Comprehensive Molecular Diagnosis of a Large Cohort of Japanese Retinitis Pigmentosa and Usher Syndrome Patients by Next-Generation Sequencing
Top Cited Papers
- 1 November 2014
- journal article
- retina
- Published by Association for Research in Vision and Ophthalmology (ARVO) in Investigative Ophthalmology & Visual Science
- Vol. 55 (11), 7369-7375
- https://doi.org/10.1167/iovs.14-15458
Abstract
Purpose.: Retinitis pigmentosa (RP), a major cause of blindness in developed countries, has multiple causative genes; its prevalence differs by ethnicity. Usher syndrome is the most common form of syndromic RP and is accompanied by hearing impairment. Although molecular diagnosis is challenging, recent technological advances such as targeted high-throughput resequencing are efficient screening tools. Methods.: We performed comprehensive molecular testing in 329 Japanese RP and Usher syndrome patients by using a custom capture panel that covered the coding exons and exon/intron boundaries of all 193 known inherited eye disease genes combined with Illumina HiSequation 2500. Candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed according to the frequency of the variants in normal populations, in silico prediction tools, and compatibility with known phenotypes or inheritance patterns. Results.: Molecular diagnoses were made in 115/317 RP patients (36.3%) and 6/12 Usher syndrome patients (50%). We identified 104 distinct mutations, including 66 novel mutations. EYS, USH2A, and RHO were common causative genes. In particular, mutations in EYS accounted for 15.0% of the autosomal recessive/simplex RP patients or 10.7% of the entire RP cohort. Among the 189 previously reported mutations detected in the current study, 55 (29.1%) were found commonly in Japanese or other public databases and were excluded from molecular diagnoses. Conclusions.: By screening a large cohort of patients, this study catalogued the genetic variations involved in RP and Usher syndrome in a Japanese population and highlighted the different distribution of causative genes among populations.This publication has 28 references indexed in Scilit:
- Next generation sequencing-based molecular diagnosis of retinitis pigmentosa: identification of a novel genotype-phenotype correlation and clinical refinementsHuman Genetics, 2013
- Next-Generation Sequencing–Based Molecular Diagnosis of a Chinese Patient Cohort With Autosomal Recessive Retinitis PigmentosaInvestigative Ophthalmology & Visual Science, 2013
- Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophiesEuropean Journal of Human Genetics, 2013
- Next-generation sequencing (NGS) as a diagnostic tool for retinal degeneration reveals a much higher detection rate in early-onset diseaseEuropean Journal of Human Genetics, 2012
- Next‐generation genetic testing for retinitis pigmentosaHuman Mutation, 2012
- Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to BiobankingCurrent Genomics, 2011
- Molecular diagnosis for heterogeneous genetic diseases with targeted high-throughput DNA sequencing applied to retinitis pigmentosaJournal of Medical Genetics, 2010
- Gene mutations in retinitis pigmentosa and their clinical implicationsClinica Chimica Acta; International Journal of Clinical Chemistry, 2004
- Digenic Retinitis Pigmentosa Due to Mutations at the Unlinked Peripherin/ RDS and ROM1 LociScience, 1994
- Mitochondrial DNA Deletions in Progressive External Ophthalmoplegia and Kearns-Sayre SyndromeThe New England Journal of Medicine, 1989