Partial duplication [dup. TCAC (178)] and novel point mutations (T125M, G188R, A209V, and H302L) of the ornithine transcarbamylase gene in congenital hyperammonemia

Human ornithine transcarbamylase (OTC) deficiency, the most prevalent genetic defect of ureagenesis, is inherited as a partially dominant X-linked trait. Affected males often die during the neonatal period with untractable hyperammonemic coma and markedly deficient enzyme activity in the liver. Nevertheless, a substantial proportion of affected males present with a late onset disease, characterized by recurrent episodes of hyperammonemia. Their OTC activity is usually partially deficient or present with abnormal kinetic properties. Heterozygous females may be symptomatic with variable severity ranging from a mere dislike of protein-containing foods to life-threatening comas. The gene encoding the human OTC has been cloned, sequenced, and mapped to chromosome Xp21.1. The OTC gene (73 kb) contains 10 exons and encodes a 354 amino acid protein. Hitherto, a number of point mutations, intragenic deletions, and large scale deletions in the OTC gene have been reported. Here, we report on the first partial duplication and describe four novel point mutations in OTC deficiency.