Targeted Next Generation Sequencing Revealed Novel PRPF31 Mutations in Autosomal Dominant Retinitis Pigmentosa.
Targeted Next Generation Sequencing Revealed Novel PRPF31 Mutations in Autosomal Dominant Retinitis Pigmentosa.
复制标题
DOI：
10.1089/gtmb.2018.0036
复制
发表时间：
2018-07
影响因子：
1.4
通讯作者：
Dan Xie;Kun Peng;Qian Yi;Wen-Ju Liu;Yeming Yang;Kuanxiang Sun;Xianjun Zhu;Fang Lu
中科院分区：
文献类型：
--
作者：
Dan Xie;Kun Peng;Qian Yi;Wen-Ju Liu;Yeming Yang;Kuanxiang Sun;Xianjun Zhu;Fang Lu
背景视网膜色素变性（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的分子诊断是具有挑战性的。目的研究2个常染色体显性遗传RP（adRP）家系和1例散发性RP患者的致病基因突变。材料与方法从参与者中获得外周血DNA样本。应用靶向下一代测序（NGS）来识别这些患者的突变。对于致病性突变分析，应用严格的NGS数据分析和分离分析。设计引物以通过桑格测序分析验证鉴定的突变。结果在PRPF 31中发现了一个新的杂合插入移码突变c.1226_1227insA，p.T410Dfs*65和一个新的杂合停止增益突变c.1015C>T，p.Q339*。在一个adRP-074家族中鉴定出已知的c.527 + 3A>G剪接突变。发现所有突变与疾病共分离，并且在500个对照样品中没有检测到这些突变。结论：我们的数据确定了PRPF 31中两个新的常染色体显性突变，扩大了该基因的突变谱。
BACKGROUND 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. AIMS This study aimed to identify the pathogenic mutations in two Chinese families with autosomal dominant RP (adRP) and in a patient with sporadic RP. MATERIALS AND METHODS 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. RESULTS A novel heterozygous insertion frameshift mutation c.1226_1227insA, p.T410Dfs*65, 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. CONCLUSIONS Our data identified two new autosomal dominant mutations in PRPF31, expanding the mutational spectrum of this gene.