Mutations and polymorphisms in the human ornithine transcarbamylase gene: Mutation update addendum

Abstract

This mutation update addendum summarizes 30 new mutations and polymorphisms found in the ornithine transcarbamylase (OTC) gene since the publication in this journal of the first mutation update. Thus, more than 60 mutations and polymorphisms in the OTC gene are currently known. Most of the mutations have been seen in a single family and the few recurrent mutations occurred in CpG dinucleotides. The presumed deleterious effects of most mutations await confirmation by appropriate expression studies. Once the tertiary structure of the enzyme is fully known, and the functional domains established, the effects of mutations, or lack thereof, could be better predicted.

Ornithine transcarbamylase deficiency: Characterization of gene mutations and polymorphisms

“…These cases confirm the well-known variability of symptoms and poor correlation of enzymatic activity in vitro with the clinical course of the disease. The substitution of lysine for threonine in codon 343 in exon 10, identified in patient 14, had recently been published by Tuchman and Plante (1995). This amino acid exchange introduces an additional positive charge and may affect the proper folding of the peptide chain although the substantial residual enzyme activity found in our patient suggests that this part of the OTC protein tolerates certain changes.…”

“…The patient's mother could be excluded as a carrier. In patient 14, a change of C to A in exon 10 resulted in the substitution of lysine for threonine in codon 343, a mutation that had been recently reported by Tuchman and Plante (1995). The mutation was not present in his mother, indicating that it had occurred spontaneously.…”

A 3‐base pair in‐frame deletion in exon 8 (delGlu272/273) of the ornithine transcarbamylase gene in late‐onset hyperammonemic coma

“…(GilbertDussardier et al, 1994(GilbertDussardier et al, , 1995Oppliger-Leibundgut et al, 1995;Tuchman and Plante, 1995).…”

Ornithine transcarbamylase deficiency: Ten new mutations and high proportion of de novo mutations in heterozygous females

“…Moreover, OTC deficiency exhibits partial dominant expression with 15 to 20% of carrier females becoming symptomatic, characterized by vomiting, lethargy and seizures and, occasionally, death (Batshaw et al, 1986). To date, about 70 distinct point mutations and several deletions of various size have been identified in the OTC gene (Tuchman and Plante, 1995). The majority of these mutations has been identified in boys.…”