毛发-鼻-指(趾)综合征一家系TRPS1基因致病突变分析

Pathogenic Mutation Analysis of TRPS1 Gene in a Family with Trichorhinophalangeal Syndrome

目的 对一异卵双胞胎同患毛发-鼻-指(趾)综合征家系进行致病基因变异检测。方法 提取该家系中双胞胎患儿及其父母和100名正常人的外周血DNA,采用二代靶向皮肤病测序包检测基因变异,并采用Sanger测序进行验证。结果 根据临床和基因检测结果,该双胞胎患儿确诊为毛发-鼻-指(趾)综合征Ⅰ型。双胞胎患儿及其母亲在TRPS1基因第4号外显子存在c.1176dupT杂合插入变异,患儿父亲及100名正常人未检出该变异,该变异的致病性已被国外文献报道。结论 毛发-鼻-指(趾)综合征Ⅰ型为常染色体显性遗传模式,该家系发病可能是由于TRPS1基因出现插入变异导致阅读框的移码而使终止密码子提前出现,产生TRPS1截短蛋白而导致。

Objective To detect pathogenic gene mutation of fraternal twins in a pedigree family of trichorhinophalangeal syndrome(TRPS).Methods DNA from peripheral blood of the twins,their parents and 100 unrelated healthy individuals were extracted.Gene mutations were detected by the skin second generation targeted sequencing kit and verified by Sanger sequencing method.Results Clinical phenotypes and the gene mutation indicated the diagnosis of TRPS type Ⅰ.Sequencing results showed an insertion mutation(c.1176dupT) in exon 4 of TRPS1 gene in the twins,which was derived from their mother,while their father and 100 unrelated individuals didn′t have the mutation.The pathogenicity of this mutation has been reported in foreign literature.Conclusion TRPS is autosomal dominant inheritance.An insertion mutation in the TRPS1 gene is predicted to result from the frameshift of reading frame and leads to the premature appearance of the stop codon,which produces a truncated TRPS1 protein.