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.