摘要目的 检测一回族近亲婚配家系Goldmann-Favre综合征患者的致病基因突变.方法 一回族近亲婚配家系2代4名成员纳入研究.采集患者和其他3名正常表型成员的外周静脉血,提取基因组DNA.应用高通量测序法筛查、Sanger测序法验证NR2E3基因突变位点.通过相关数据库和PubMed文献检索基因突变位点的致病性报道,通过蛋白质预测软件阐释其功能.结果 患者存在NR2E3基因c.925C＞T(p.R309W)错义突变,该纯合突变导致其编码的光感受器特异的视网膜核受体第309位氨基酸由精氨酸变为色氨酸.患者父母分别为NR2E3基因c.925C＞T(p.R309W)杂合突变携带者.NR2E3基因产物蛋白309氨基酸位点在物种间具有高度保守性,蛋白质预测软件预测该变异为有害突变.结论 NR2E3基因c.925C＞T(p.R309W)位点纯合突变是该患者的致病基因.

abstractsObjective To identify the pathogenic genes and mutations in a Hui population family with Goldmann-Favre syndrome.Methods A two-generation Hui population family with consanguineous marriage including 4 individuals was enrolled in this study.DNA was extracted from 4 ml peripheral venous blood of all participants.The DNA sequence was performed by Ophthalmology Gene panel sequencing through Ion PGM platform.Then the selected mutations were proved by PCR-Sanger sequencing method.Pathogenic analysis of the mutation was done by means of retrieving PubMed and related databases.And the function of mutation effect was interpreted by protein prediction software.Results The sequence result showed that a novel homozygous mutation in NR2E3,c.925C ＞ T (p.R309W),which resulted in conversion of arginine to tryptophan at position 309 of the photoreceptor-specific retinal nuclear receptor.Parents of the proband were carriers of the heterozygous mutation.The 309 amino acid locus of NR2E3 protein product was highly conserved among species,and protein prediction softwares predicted the mutation as harmful.Conclusion The homozygous mutation c.925C＞T (p.R309W) in NR2E3 cause Goldmann-Favre syndrome in this patient.