A SPLICING MUTATION, A NONSENSE MUTATION (Y167X) AND 2 MISSENSE MUTATIONS (I159T AND A209V) IN SPANISH PATIENTS WITH ORNITHINE TRANSCARBAMYLASE DEFICIENCY

Four novel mutations are identified in the ornithine transcarbamylase (OTC) gene, in four patients with OTC deficiency (an X-linked disorder ). The mutations represent three different categories: missense (Ile15 9Thr and Ala209Val), nonsense (Sr167Stop), and causing inefficient spl icing (G-->A in the first intronic base) with associated aberrant spli cing. They are located in exons 5, and 6, and in intron 3. Two Of the mutations arose de novo in the patients, and only one mutation occurs at a CpG site. The nonsense and the splicing mutation cause, respectiv ely, lethal early onset and non-lethal, delayed early onset clinical p resentations in males. Our results confirm for Spain the high genotypi c heterogeneity of OTC deficiency.