一例新生儿瓜氨酸血症Ⅰ型ASS1基因突变分析

ASS1 gene mutation in a neonate with citrullinemia typeⅠ

目的对一例新生儿筛查出的疑似瓜氨酸血症(citrullinemia)的患儿进行串联质谱和基因检测,并对其父母进行基因突变检测,以明确其诊断并进行随访。方法用串联质谱检测技术(MS/MS),对新生儿进行遗传代谢病筛查,对筛查出的疑似瓜氨酸血症的患儿采集外周血检测遗传代谢病产物,采集患儿及其父母外周血进行高通量测序和Sanger测序,对患儿及其父母的血样进行测序验证,进而对基因异常进行分析。结果该患儿瓜氨酸显著升高,为1043μmol/L,立即召回,复查瓜氨酸数值升高到2072μmol/L。检测到患儿ASS1基因有c.256C>T和c.577G>A两个杂合突变,分别遗传自父亲和母亲,确诊为瓜氨酸血症Ⅰ型。结论对新生儿进行串联质谱分析筛查,及对疑似患儿进一步基因测序分析,有助于瓜氨酸血症的诊断。

Objective To detect blood acylcarnitine and genes in a newborn with suspected citrullinemia,and to detect gene mutations in their parents,so as to clarify their diagnosis and follow-up investigations.Methods Genetic metabolic diseases were screened in the newborn baby using tandem mass spectrometry.Peripheral blood samples were collected from the newborn patient with suspected citrullinemia to detect the products of genetic metabolic diseases.Peripheral blood samples were collected from newborns and their parents for high-throughput sequencing and Sanger sequencing.The blood samples of the newborns and their parents were sequenced and verified,and then the genetic abnormalities were analyzed.Results Tandem mass spectrometry showed that the level of citrulline increased(1043μmol/L),the level of citrulline increased to 2072μmol/L after recall immediately.Double heterozygous mutations of ASS1 gene in the proband were identified:c.256C>T and c.577G>A,which were confirmed in the parents.The case was diagnosed with citrullinemia typeⅠ.Conclusions Neonatal tandem mass spectrometry,in combination with a pedigree analysis of the gene sequencing,may support the diagnosis of citrullinemia.