Mutation spectrum of the ASS1 gene in Korean patients with citrullinemia type I

Objectives: Citrullinemia type I is a rare metabolic disorder and the distribution of mutations in the ASS1 gene varies among ethnic groups. We aimed to determine the molecular characteristics of citrullinemia type I in Korean patients. Design and methods: Biochemical and clinical findings were investigated and mutations in the ASS1 gene were identified using direct sequencing method in five patients with high citrulline levels. We also reviewed previous genotypes reported for Korean patients with citrullinemia type I. Results: We identified five mutations in 10 mutant alleles from the five patients. The most common mutation was the Gly324Ser mutation, which was present in 40% of the mutant alleles, followed by the c.421-2A>G mutation (30% of the mutant alleles). The other mutations (c.1128-6_1188dup67, Arg127Gln, and Arg279Gln) were identified in one mutant allele each. A comprehensive review of previous Korean reports revealed that Gly324Ser, c.421-2A>G, and c.1128-6_1188dup67 mutations accounted for 80.8% of the total mutations reported to date. In terms of genotype–phenotype correlations, a patient homozygous for the c.421-2A>G mutation had fatal clinical manifestations and two patients who were compound heterozygous for the Gly324Ser and c.1128-6_1188dup67 mutations presented with a mild clinical course. Conclusion: We provided important information about the mutational spectrum of ASS1 gene in Korean patients with citrullinemia type I and demonstrated a difference in common mutations in the ASS1 gene according to ethnic and geographic backgrounds. [ABSTRACT FROM AUTHOR]