关键词: 瓜氨酸血症Ⅰ型； ASS1基因； 变异； 生物信息学分析

Abstract: Objective To explore the genetic variation characteristics of citrullinemia type Ⅰ in a neonate family. Methods The clinical data of citrullinemia type Ⅰ in 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 ASS1 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 ASS1 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 ASS1 gene variant spectrum in Chinese neonates.

Key words: citrullinemia typeⅠ; ASS1 gene; mutation; bioinformatics analysis