青岛大学学报（医学版）2026，Vol.62Issue(3)：423-427,5.DOI:10.11712/jms.2096-5532.2026.62.079
瓜氨酸血症Ⅰ型一家系ASS1基因变异分析
ASS1 gene mutation in a Chinese family with citrullinemia type Ⅰ
摘要
Abstract
Objective To investigate the suspected pathogenic genes in the family of a child with citrullinemia type Ⅰ(CTLN1)and the genotype-phenotype relationship in this case.Methods Whole-genome DNA was extracted from the heel blood of the child and the peripheral venous blood of the parents,and whole exome sequencing(WES)and Sanger sequencing were used for gene mutation testing and family validation.The bioinformatics methods were used to analyze the pathogenicity of candi-date gene mutations.Results WES showed that the child carried biallelic compound heterozygous mutations in the ASS1 gene,i.e.,ASS1-C.970+5G＞A and ASS1-C.1142G＞A(p.G381D),among which ASS1-C.1142G＞A(p.G381D)was a novel heterozy-gous mutation.Sanger sequencing confirmed that the father of the child carried the ASS1-c.970+5G＞A heterozygous mutation,and the mother of the child carried the ASS1-c.1142G＞A(p.G381D)heterozygous mutation.According to the mutation-related guidelines by the American College of Medical Genetics and Genomics,ASS1-c.970+5G＞A mutation was rated as a pathogenic mutation(PS3+PM2_P+PM3_S+PP4),and ASS1-c.1142G＞A(p.G381D)mutation was rated as a mutation with unknown clinical significance(PM2_P+PM3_P+PP4).Conclusion The biallelic compound heterozygous mutations of ASS1-c.970+5G＞A and ASS1-c.1142G＞A(p.G381D)may be the pathogenic mutation sites in this child with CTLN1.This study enriches the mutation spectrum of the ASS1 gene and provides a basis for the genetic counseling and prenatal diagnosis of CTLN1.关键词
瓜氨酸血症/基因/突变/遗传关联研究/全外显子组测序Key words
citrullinemia/genes/mutation/genetic association studies/whole exome sequencing分类
医药卫生引用本文复制引用
郑璇,邹卉,李玲,张仁伟,刘世国..瓜氨酸血症Ⅰ型一家系ASS1基因变异分析[J].青岛大学学报（医学版）,2026,62(3):423-427,5.基金项目
国家自然科学基金项目(82071683) （82071683）
