新生儿瓜氨酸血症Ⅰ型一家系基因分析

Genetic analysis of citrullinemia type Ⅰ in a neonate family

目的分析新生儿瓜氨酸血症Ⅰ型家系的基因变异特征。方法回顾分析1例新生儿瓜氨酸血症Ⅰ型患儿的临床资料,提取患儿及其父母外周血基因组DNA,采用二代测序技术进行基因检测,Sanger测序、生物信息学分析和定量PCR进一步验证测序结果。结果女性患儿,出生后反应差、四肢不规则抖动、肌张力增高,逐渐出现呼吸衰竭;血氨、血乳酸升高,血糖降低。血串联质谱检查提示瓜氨酸显著增高,尿气相色谱质谱检查提示尿乳清酸显著增高。基因检测发现患儿ASS 1基因c.1194-2A>G和3号外显子缺失复合杂合变异,其中c.1194-2A>G遗传自父亲,3号外显子缺失遗传自母亲,两种变异在HGMD数据库中均未报道,根据ACMG指南划分为可能致病性变异。结论ASS1基因c.1194-2A>G杂合变异和3号外显子杂合缺失是该新生儿瓜氨酸血症Ⅰ型的遗传学病因,丰富了中国人新生儿ASS 1基因变异谱。

Objective To explore the genetic variation characteristics of citrullinemia typeⅠin a neonate family.Methods The clinical data of citrullinemia typeⅠin a neonate were retrospectively analyzed.Genomic DNA was extracted from the peripheral blood of the child and her parents.Gene detection was performed by second-generation sequencing technology.Sanger sequencing,bioinformatics analysis and quantitative PCR were used to further verify the sequencing results.Results One female neonate had poor reaction,irregular shaking of limbs,increased muscle tension and gradually developed respiratory failure after birth.At the same time,the blood ammonia and lactic acid increased and the blood glucose decreased.Blood mass spectrometry showed a significant increase in citrulline,and urine gas chromatography-mass spectrometry showed a significant increase in urinary whey acid.Gene detection revealed that the neonate's ASS 1 gene had c.1194-2 A>G heterozygous variant which was inherited from the father and heterozygous deletion of exon 3 which c.1194-2 A>G was inherited from the mother.These two variants were not reported in HGMD database.According to ACMG guidelines,they were classified as possible pathogenic variants.Conclusion ASS 1 gene c.1194-2 A>G heterozygous variant and exon 3 heterozygous deletion are the genetic causes of the neonatal citrullinemia typeⅠ,which enriches the ASS 1 gene variant spectrum in Chinese neonates.