新生儿瓜氨酸血症Ⅰ型一例ASS1基因突变研究

ASS1 gene mutation in a neonate with citrullinemia type Ⅰ

目的 对1例瓜氨酸血症Ⅰ型家系进行基因检测,阐明其病因,为该病的诊断和遗传咨询提供依据.方法 提取患儿及其父母外周血基因组DNA,采用Sanger测序对ASS1基因14个外显子进行DNA测序,Phyre软件分析ASS1蛋白分子的三级结构及功能.结果 检测到患儿有c.951delT （F317LfsX375）和c.1087C ＞T （R363W）两个杂合突变,分别遗传自父亲和母亲.蛋白质结构分析发现,c.951 delT影响ASS1蛋白分子的空间结构和功能.结论 ASS1基因c.951 delT和c.1087C＞T复合杂合突变是导致患儿瓜氨酸血症Ⅰ型的分子病因,c.951 delT为未见报道的突变类型,推测其改变了蛋白质分子的空间构型,从而影响ASS1蛋白的酶活性.

Objective To identify the genetic mutation in ASS1 gene in a Chinese family with citrullinemia type Ⅰ,which may provide a basis for the diagnosis and genetic counseling.Method Genomic DNA was isolated from peripheral blood samples of the family members.Mutation analysis of ASS1 gene was carried out by PCR and Sanger sequencing.Biostructural analysis of the mutated ASS1 was completed by Phyre server.Result Double heterozygous mutations in the proband were identified：c.951delT （F317LfsX375） and c.1087C 〉 T （R363W）,which were confirmed in the proband＇s father and mother,respectively.It was found that the c.951delT mutation might change the formation of a dimer or a tetramer and the function of ASS1 protein.Conclusion Double heterozygous mutations for c.951delT and c.1087C 〉T have been found in a proband with citrullinemia type Ⅰ.The c.951delT is a novel mutation in citrullinemia type Ⅰ,which may change the configuration of ASS1 protein and result in ASS1 dysfunction.