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Ornithine transcarbamylase deficiency: Characterization of gene mutations and polymorphisms
Author(s) -
Leibundgut Elisabeth Oppliger,
Wermuth Bendicht,
Colombo JeanPierre,
LiechtiGallati Sabina
Publication year - 1996
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1996)8:4<333::aid-humu6>3.0.co;2-8
Subject(s) - missense mutation , biology , ornithine transcarbamylase , exon , genetics , ornithine transcarbamylase deficiency , allele , microbiology and biotechnology , mutation , gene , intron , urea cycle , arginine , amino acid
We identified three new and three known mutations in male patients with OTC deficiency using PCR amplification of all the individual exons, including the adjacent intron sequences, followed by direct sequencing of the amplimers. Two mutations were found in males presenting with neonatal fatal hyperammonemia and no detectable enzyme activity in their livers. The H302Y mutation found in one patient affects the putative binding site for ornithine. The second patient had an R141X mutation, which is one of the few recurrent mutations in the OTC gene. Four different missense mutations were identified in male patients with late onset of the disease and residual OTC activities between 14% and 35%. The mutations are Y176C and P220A and the known mutations K88N and T343K, respectively. Four of the patients' mothers were identified as carriers. In two cases, the mutations had occurred spontaneously. In addition, the frequency of four polymorphisms of the OTC gene was studied. The K46R polymorphism in exon 2 and the Q270R polymorphism in exon 8 were found in 36% and 4% of screened alleles, respectively. Two questionable polymorphisms in exon 4, F101L and L111P, were not present in any of the screened alleles. © 1996 Wiley‐Liss, Inc.