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Identification of new mutations in the ornithine transcarbamylase (OTC) gene in Korean families
Author(s) -
Yoo H.W.,
Kim G.H.,
Lee D.H.
Publication year - 1996
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/bf01799346
Subject(s) - ornithine transcarbamylase , genetics , human genetics , gene , ornithine transcarbamylase deficiency , identification (biology) , mutation , ornithine carbamoyltransferase , biology , metabolic disease , medicine , ornithine , urea cycle , endocrinology , amino acid , arginine , botany
Summary Ornithine transcarbamylase (OTC) deficiency, an X‐linked inborn error of the urea cycle, is known to be heterogeneous genetically as well as phenotypically. Molecular defects of Korean patients with OTC deficiency have not been reported. To investigate molecular lesions resulting in OTC deficiency, the OTC genes of unrelated symptomatic or asymptomatic female heterozygotes were amplified exon by exon and analysed by direct sequencing of double‐stranded DNA. Three new mutations, two missense and one nonsense, were detected: (1) a C‐to‐T transition in codon 44 in exon 2 replacing a threonine by an isoleucine (T44I) was found in a late‐onset symptomatic female patient but not in her asymptomatic mother; (2) a C‐to‐T transition in codon 214 creating a new Rsa I recognition site in exon 6 and substituting tyrosine for histidine (H214Y) was identified in an asymptomatic female carrier whose son developed acute neonatal onset of OTC deficiency; (3) a C‐to‐T transition in codon 320 (arginine) abolishing a Taq I recognition site and creating a new BCl I site in exon 9 with generation of a stop codon (R320X) leading to premature termination in the enzyme. This nonsense mutation was found in a symptomatic female patient and her asymptomatic mother whose son died of OTC deficiency during the neonatal period. In addition, we found a G‐to‐A transition in codon 141 in exon 5 causing substitution of glutamine for arginine (R141Q) in a female obligate heterozygote whose previous three sons succumbed to acute neonatal‐onset OTC deficiency. This missense mutation has been described previously and is known to eliminate a Taq I recognition site in exon 5.