【摘要】 目的 检测近亲结婚Leber先天性黑矇(LCA)家系致病基因突变。方法 选择近亲结婚Leber先天性黑矇家系作为研究对象，收集家系成员眼科检查资料和病史，采集外周静脉血，提取DNA。先证者采用全基因组外显子测序技术进行致病基因突变筛查；通过生物信息学分析后得到候选致病突变位点。运用Sanger测序进行验证及家系共分离分析，确定致病性突变位点。结果 基因检测在先证者TULP1基因(MIM#602280)第11号外显子检测到新的纯和错义突变c.C1024G(p.R342G),编码区第1024位的核苷酸C(胞嘧啶)变异为G(鸟嘌呤),变异导致编码蛋白序列内的氨基酸改变p.R342G,第342号氨基酸由精氨酸(Arg)变异为甘氨酸(Gly)。342号氨基酸位点在不同物种间具有高度保守性。生物学信息预测提示为致病性。结论 TULP1基因纯和错义突变c.C1024G:p.R342G是该家系的致病原因。该纯合突变国内外均未见报道，是一种新发现的LCA致病基因突变。本研究扩大了LCA基因突变谱，为LCA基因治疗及发病机制研究提供了依据。更多还原

【Abstract】 Objective To identify the pathogenic gene mutation in a consanguineous family with Leber Congenital Amaurosis(LCA).Methods A Leber congenital amaurosis family was selected as the research object. Related ophthalmologic examination were collected and genomic DNA was extracted. The family was investigated with a specific hereditary eye disease enrichment panel(HEDEP) based on exome sequencing technology. The identified variant was confirmed with Sanger sequencing Potential(SNP). Potential pathogenic mutation was analyzed using software and conserved domain analysis and performed co-separated analysis between the family member and the proband.Results The sequence result showed that the proband carried pure and missense mutation in the TULP1 gene: c.C1024G in exon 11.Conclusion The pure and missense mutation of c.C1024G in TULP1 is responsible for LCA pathogenesis in this Chinese pedigree. The c.C1024G mutations in LCA have not been reported in the literature and database.更多还原