一个导致视网膜色素变性的RHO基因新突变的鉴定  

Identification of a novel RHO mutation in a pedigree affected with retinitis pigmentosa

作　　者：白周现 刘莉娜 胡爽 吴庆华[1] 孔祥东[1] Bai Zhouxian;Liu Lina;Hu Shuang;Wu Qinghua;Kong Xiangdong(Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, China)

机构地区：[1]郑州大学第一附属医院遗传与产前诊断中心,450000

出　　处：《中华医学遗传学杂志》2019年第3期234-237,共4页Chinese Journal of Medical Genetics

基　　金：郑州大学第一附属医院青年创新基金(YNQN2017008).

摘　　要：目的检测1个视网膜色素变性大家系的致病基因突变。方法收集该家系患者和正常表型成员的临床资料,采集外周血提取基因组DNA。应用高通量测序法筛查、Sanger测序法验证RHO基因新突变位点。在对照人群中筛查该突变。结果该家系患者中存在RHO基因c.251T>C(p.Leu84Pro)错义突变,该突变导致其编码蛋白视紫红质第84位氨基酸由亮氨酸变为脯氨酸(p.Leu84Pro)。在家系正常成员和831例对照人群中未检测到这个突变。该突变在ExAC、1000G、dbSNP等数据库中亦未见收录。SIFT、PolyPhen_2、Mutation t@sting 3款蛋白预测软件均预测该突变为有害。结论RHO基因c.251T>C(p.Leu84Pro)错义突变是该家系的致病原因,据此突变位点可进行产前诊断。Objective To identify the pathogenic mutation underlying retinitis pigmentosa in a large pedigree. Methods The pedigree has included three generations showing an autosomal dominant transmission of retinitis pigmentosa. Potential mutations were screened using a retinitis pigmentosa gene panel and an Ion PGM platform. Suspected mutation was verified by Sanger sequencing. Results A novel heterozygous missense mutation, c. 251T>C(p.Leu84Pro), was identified in the RHO gene. The mutation has co-segregated with the retinitis pigmentosa phenotype among all family members and was not found in public databases ExAC, 1000G and dbSNP or 831 healthy controls. The mutation was predicted to be damaging by three major protein-predicting software. Conclusion The c. 251T>C (p.Leu84Pro) mutation of the RHO gene is a novel pathogenic mutation underlying the retinitis pigmentosa phenotype in this pedigree. Above findings have enabled prenatal diagnosis for the pedigree.

关 键 词：视网膜色素变性 RHO基因 新发突变 致病性分析 

分 类 号：R774.1[医药卫生—眼科] R440[医药卫生—临床医学]