Mutation screening in genes known to be responsible for Retinitis Pigmentosa in 98 Small Han Chinese Families

Lulin Huang,Qi Zhang,Jiyun Yang,Yao Mao,Chang Tan,Peiquan Zhao,Shi Ma,Yuanfeng Li,You Li,Chao Qu,Zhenglin Yang,Xin Huang

doi:10.1038/s41598-017-00963-6

Abstract

Retinitis pigmentosa (RP) is highly heterogeneous in both clinical and genetic fields. Accurate mutation screening is very beneficial in improving clinical diagnosis and gene-specific treatment of RP patients. The reason for the difficulties in genetic diagnosis of RP is that the ethnic-specific mutation databases that contain both clinical and genetic information are largely insufficient. In this study, we recruited 98 small Han Chinese families clinically diagnosed as RP, including of 22 dominant, 19 recessive, 52 sporadic, and five X-linked. We then used whole exome sequencing (WES) analysis to detect mutations in the genes known for RP in 101 samples from these 98 families. In total, we identified 57 potential pathogenic mutations in 40 of the 98 (41%) families in 22 known RP genes, including 45 novel mutations. We detected mutations in 13 of the 22 (59%) typical autosomal dominant families, 8 of the 19 (42%) typical autosomal recessive families, 16 of the 52 (31%) sporadic small families, and four of the five (80%) X-linked families. Our results extended the mutation spectrum of known RP genes in Han Chinese, thus making a contribution to RP gene diagnosis and the pathogenetic study of RP genes.

Highlights

Retinitis pigmentosa (RP) exhibits autosomal dominant, autosomal recessive, or X-linked models
Similar studies in RP have been published in the last few years, most of these reports were focused on the Caucasian population
We investigated the mutations of known RP genes in 101 patients in 98 small Han Chinese RP families, which is beneficial for RP gene diagnosis and the pathogenic study of RP

Summary

Introduction

RP exhibits autosomal dominant (adRP), autosomal recessive (arRP), or X-linked (xlRP) models. The cause is a digenic pattern of inheritance. Autosomal recessive, and X-linked account for approximately 30–40%, 50–60%, and 5–15% respectively of patients with RP2. 30% are sporadic cases[4], most of which may belong to the autosomal recessive inheritance group. Similar studies in RP have been published in the last few years, most of these reports were focused on the Caucasian population. Published RP mutations in the Chinese population are rare in the Human Gene Mutation Database (HGMD, http://www.hgmd.org/) and the Online Mendelian Inheritance in Man (OMIM, http://omim.org/). Different populations may have different mutation spectra, which is very important in studying the origin and pathogenesis of heterogeneous diseases such as RP. We investigated the mutations of known RP genes in 101 patients in 98 small Han Chinese RP families, which is beneficial for RP gene diagnosis and the pathogenic study of RP

Methods

Results

Conclusion