An Adenine Insertion between Nucleotide Positions 4957 and 4958 in the EYS Gene Is a Possible Major Cause of arRP in the Japanese Population

Abstract

Purpose: : Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease including autosomal recessive (ar), autosomal dominant (ad), and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog), which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients.

Methods: : To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed.

Results: : We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study is 18% (18/100, with 9 of 18 patients bearing very likely pathogenic mutations having single mutations). In addition, a novel insertion, c.4957_4958insA, was detected in 12 patients.

Conclusions: : This report is the first molecular genetic analysis of the EYS gene in a cohort of unrelated Japanese RP patients. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population, and that 66.7% (12/18 cases) distinct EYS gene mutations are due to the one-base insertion.

Keywords: genetics • retinitis • mutations