PMID: 18204299Jan 22, 2008Paper

Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation

The Kobe Journal of Medical Sciences
Wakako OginoMasafumi Matsuo

Abstract

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. Although a combination of molecular methods have been used including DNA sequencing of all 10 exons and exon-intron boundaries of OTC gene, only approximately 80% of patients with OTC deficiency are found to have mutations. We report two known and three novel mutations of the OTC gene in five Japanese patients including two neonatal-onset, one late-onset, and two symptomatic female patients. Known nonsense mutations (c.578G>A and c.421C>T) were detected in a neonatal-onset male and a symptomatic female patient, respectively. Mutation analysis revealed two novel mutations including one splice site mutation (c.386+1G>C) in a symptomatic female patient and one missense mutation (c.515T>A) in a late-onset male patient. In the remaining case, which was a neonatal-onset male patient, no mutation was disclosed by direct sequencing of all 10 exons and their flanking intron sequences. Therefore, OTC mRNA in the liver was analyzed by RT-PCR, and remarkably, a 135-nt insertion was detected between exons 5 and 6. Genomic DNA analysis of intron sequences revealed a single nucleotide change at 265 bp downstream from the 3' end of exon 5, which crea...Continue Reading

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