TMEM67基因突变所致的Joubert综合征一家系及临床遗传学分析 [中文引用][英文引用]

目的 利用二代测序技术结合Sanger测序验证对一临床诊断为Joubert综合征的家系进行致病基因检测。方法 以2015年广东省妇幼保健院产前诊断科诊断为Joubert综合征的一家系为研究对象，采集先证者胎儿病史、影像学检查结果及家族史，采用全外显子高通量测序方法，对先证者胎儿及其父母进行基因检测，后对发现的致病位点进行Sanger测序验证。结果 检测到先证者在TMEM67基因第12个外显子上发生了错义突变，c.1175C>G（来源于父亲），以及在TMEM67基因第12个外显子上发生了另外一个错义突变，c.1250A>G（来源于母亲）的双重杂合改变，符合孟德尔隐性遗传。结论 本研究成功利用二代测序技术鉴定了一种导致Joubert综合征的新发突变类型，此位点为国内外首次报道，丰富了Joubert综合征的病因信息。二代测序技术为产前确诊罕见疾病提供一套可行的新方法，建立基因水平上的堡垒。

Objective Using next-generation sequencing (NGS) and Sanger sequencing to detect the novel gene mutation in a Joubert syndrome family. Methods A family which diagnosed as Joubert syndrome family was enrolled as subject of this study from our outpatients in 2015. Following the medical history, imaging results and family history of the suffering fetus, next-generation sequencing (NGS) and sanger sequencing were used for suffering fetus and its parents to detect and verify the gene mutation causing this disease. Results A missense mutation c.1175C>G (inherited from father)，and another missense mutation c.1250A>G (inherited from father)had been identified in the affected fetus, which had been confirmed to accord with Mendelian inheritance．Conclusions We firstly described a mutation in gene TMEM67, which is a novel mutation causing Joubert syndrome. This discovery had enriched the gene information of Joubert syndrome and next-generation sequencing (NGS) provided a practical method for prenatal diagnosis of rare disease.