Mutation screening of the USH2A gene in retinitis pigmentosa and USHER patients in a Han Chinese population

Lulin Huang,Jiyun Yang,Zhenglin Yang,Yao Mao,Yuanfeng Li,Yang Li

doi:10.1038/s41433-018-0130-3

Abstract

ObjectivesUSH2A encodes for usherin, a basement membrane protein in the inner ear and retina. USH2A can cause retinitis pigmentosa (RP) with or without hearing loss. The aim of this study was to detect USH2A mutations in a Chinese cohort of 75 small RP families and 10 Usher syndrome families.MethodsWe performed a direct Sanger sequencing analysis of the USH2A gene to identify mutations for this cohort.ResultsWe identified a total of eight mutations in four of the 75 small RP families (5.3%) and two mutations in one of the 10 Usher families (10%); all families were detected to have compound heterozygous mutations. In families with nonsyndromic RP, we identified the compound heterozygous mutations p.Pro4818Leuand p.Leu2395Hisfs*19 in family No. 19114, p.Arg4493His and p.His1677Glnfs*15 in family No.19162, c.8559-2A > G and p.Arg1549* in family No.19123 and p.Ser5060Pro and p.Arg34Leufs*41 in family No.19178. We also identified the heterozygous mutations p.Arg3719His and p.Cys934Trp in family No.19124, which was the Usher syndrome family. These mutations were predicted to be harmful by SIFT, PROVEAN, Mutation Taster or PolyPhen-2.ConclusionsOur results revealed six novel mutations in the USH2A gene in a Chinese population, which is beneficial for the clinical use of genetic testing of USH2A in patients with autosomal-recessive or sporadic RP and Usher syndrome.

Highlights

IntroductionRetinitis pigmentosa (RP, OMIM 226800) is one of the most common incurable eye diseases [1, 2] and has clinical and genetic heterogeneity [3, 4]
These authors contributed : Lulin Huang, Yao Mao, Yang Li, Zhenglin Yang.Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Retinitis pigmentosa (RP, OMIM 226800) is one of the most common incurable eye diseases [1, 2] and has clinical and genetic heterogeneity [3, 4]
We identified six novel mutations in the USH2A gene causing nonsyndromic retinitis pigmentosa (RP) or Usher syndrome in a Chinese population; this finding provides a theoretical basis for follow-up research and treatment of this disease

Summary

Introduction

Retinitis pigmentosa (RP, OMIM 226800) is one of the most common incurable eye diseases [1, 2] and has clinical and genetic heterogeneity [3, 4]. RP can be inherited as autosomal dominant (30–40%), autosomal recessive (50–60%), or X-linked (5–15%) [5, 6]. 87 genes have been identified as responsible for RP (https:// sph.uth.edu/retnet/sum-dis.htm), including 27 genes for autosomal dominant RP, 57 genes for autosomal recessive RP, and three genes for X-linked RP. The most common syndromic RP is Usher syndrome, which accompanies RP with hearing loss in autosomal recessive inheritance, with a prevalence of approximately 1:20,000 [7]. Thirteen genes have been identified that may cause Usher syndrome Thirteen genes have been identified that may cause Usher syndrome (https://sph.uth. edu/retnet/sum-dis.htm)

Objectives

Methods

Results

Conclusion