瓜氨酸血症I型三个家系的临床及ASS1基因变异分析

Clinical and ASS1 gene variant analysis of three Chinese pedigrees affected with Citrullinemia type I

目的对3个瓜氨酸血症I型(CTLN1)家系进行基因分析,总结中国CTLN1的临床和遗传学特征。方法将2017年至2020年就诊于山东大学附属儿童医院的3例患儿作为研究对象。采集3例患儿及父母的外周血样,对其DNA进行全外显子组测序,并对候选变异进行Sanger测序家系验证和致病性分析。结果3例患儿分别携带ASS1基因c.207_209delGGA和c.1168G>A、c.349G>A和c.364-1G>A、c.470G>A和c.970G>A复合杂合变异,其中c.207_209delGGA、c.364-1G>A既往未见报道。患儿父母均为杂合携带者。结论新发现的c.207_209delGGA、c.364-1G>A变异扩大了ASS1基因的变异谱。中国CTLN1患者的变异谱具有异质性。

Objective To analyze the clinical and genetic characteristics of three Chinese pedigrees affected with Citrullinemia type I(CTLN1).Methods Three children diagnosed at the Children's Hospital Affiliated to Shandong University from 2017 to 2020 were selected as the study subjects.Genomic DNA was extracted from peripheral blood samples of the probands and their parents.Next generation sequencing(NGS)was carried out to detect pathological variants of the probands.Sanger sequencing was used for validating the candidate variant among the pedigrees.Results The probands have respectively carried compound heterozygous variants of c.207_209delGGA and c.1168G>A,c.349G>A and c.364-1G>A,c.470G>A and c.970G>A of the ASS1 gene,which were respectively inherited from their parents.Conclusion The newly discovered c.207_209delGGA and c.364-1G>A variants have enriched the mutational spectrum of the ASS1 gene.And the mutation spectrum of Chinese CTLN1 patients is heterogeneous.