Xie Dan, Peng Kun, Yi Qian, Liu Wenjinag, Yang Yeming, Sun Kuanxiang, Zhu Xianjun, Lu Fang
1 Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China , Chengdu, Sichuan, China .
2 Department of Laboratory Medicine, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan Translational Medicine Research Hospital , Chengdu, Sichuan, China .
Genet Test Mol Biomarkers. 2018 Jul;22(7):425-432. doi: 10.1089/gtmb.2018.0036. Epub 2018 Jun 29.
Retinitis pigmentosa (RP) is a rare type of inherited retinal dystrophy that can result in progressive vision loss. Molecular diagnosis of RP is challenging due to phenotypic and genotypic heterogeneities.
This study aimed to identify the pathogenic mutations in two Chinese families with autosomal dominant RP (adRP) and in a patient with sporadic RP.
Peripheral blood DNA samples were obtained from the participants. Targeted next generation sequencing (NGS) was applied to identify mutations in these patients. For pathogenic mutation analyses, stringent NGS data analyses and segregation analyses were applied. Primers were designed to validate the identified mutations by Sanger sequencing analyses.
A novel heterozygous insertion frameshift mutation c.1226_1227insA, p.T410Dfs65, and a novel heterozygous stopgain mutation c.1015C>T, p.Q339 were identified in PRPF31. A known c.527 + 3A>G splicing mutation was identified in one of the adRP-074 families. All mutations were found to co-segregate with the disease, and none of these mutations were detected in 500 control samples.
Our data identified two new autosomal dominant mutations in PRPF31, expanding the mutational spectrum of this gene.
视网膜色素变性（RP）是一种罕见的遗传性视网膜营养不良，可导致进行性视力丧失。由于表型和基因型的异质性，RP的分子诊断具有挑战性。
本研究旨在鉴定两个常染色体显性RP（adRP）中国家系及一名散发性RP患者的致病突变。
从参与者获取外周血DNA样本。应用靶向二代测序（NGS）鉴定这些患者的突变。对于致病突变分析，应用严格的NGS数据分析和分离分析。设计引物通过桑格测序分析验证鉴定出的突变。
在PRPF31中鉴定出一个新的杂合插入移码突变c.1226_1227insA，p.T410Dfs65，以及一个新的杂合无义突变c.1015C>T，p.Q339。在adRP-074家系之一中鉴定出一个已知的c.527+3A>G剪接突变。所有突变均与疾病共分离，且在500份对照样本中未检测到这些突变中的任何一个。
我们的数据在PRPF31中鉴定出两个新的常染色体显性突变，扩展了该基因的突变谱。
