Four newly identified ornithine transcarbamylase (OTC) mutations (D126G, R129H, I172M and W332X) in Japanese male patients with early-onset OTC deficiency

Ornithine transcarbamylase (OTC) (EC 2.1.3.3) deficiency is an X-linked urea cycle disorder. Hemizygotes with neonatal onset mostly die within 1 month of life, with hyperammonemic coma, as a result of extremely low activity of OTC in the liver. Female heterozygotes have a wide range of manifestations from an asymptomatic status to mild or severe symptoms, depending on lyonization and allelic heterogeneity. There are known heterozygous mutations of the OTC allele, including deletion, point mutation in exons, and point mutation in introns that resulted in splicing abnormality. We report here four novel OTC mutant alleles in Japanese male patients with early-onset disease, identified using the polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) method. Gene tracking was also done for three of the four families.