Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive disorder of the urea cycle caused by a deficiency in the argininosuccinate synthetase (ASS1) enzyme due to mutations in the ASS1 gene. Only a few Chinese patients with CTLN1 have been reported, and ASS1 gene mutations have been identified sporadically in China.
Case presentation: A Chinese family with one member affected with mild CTLN1 was enrolled. Targeted exome sequencing was performed on the proband, and Sanger sequencing was used to validate the detected mutation. We also reviewed the genetic and clinical characteristics of CTLN1 in Chinese patients that have been published to date. Newborn screening showed remarkably increased concentrations of citrulline with elevated ratios of citrulline/arginine and citrulline/phenylalanine, and the patient presented with a speech delay at age three. The urinary organic acid profiles were normal. A novel homozygous splicing variant c.773 + 4A > C in the ASS1 gene was identified in the proband, and it was predicted to affect splicing by in silico analysis. To date, only nine Chinese patients with CTLN1 have been reported, with a total of 15 ASS1 mutations identified and no high frequency or hot spot mutations found; the mutation spectrum of Chinese patients with CTLN1 was heterogeneous.
Conclusions: We described a mild Chinese CTLN1 case with a novel homozygous splicing variant c.773 + 4A > C and reviewed previous genotypes and phenotypes in Chinese patients with CTLN1. Thus, our findings contribute to understanding the molecular genetic background and clinical phenotype of CTLN1 in this population.
Keywords: ASS1; Citrullinemia type I; Mutation spectrum; Novel variant.