title: Phenotypic variability in male patients carrying the mutant ornithine transcarbamylase (OTC) allele, Arg40His, ranging from a child with an unfavourable prognosis to an asymptomatic older adult.
abstract: In five different Japanese families, we identified six male hemizygotes (aged 6, 9, 15, 17, 56, and 65 years) and a putative candidate (aged 48 years), carrying a mutant allele of the ornithine transcarbamylase (OTC) gene, a G to A substitution at nucleotide 119 in exon 2 generating histidine in place of arginine. OTC activity in the necropsied liver tissue was reduced to approximately 12% of the control and that of COS 1 cells transfected with Arg40His OTC cDNA was 10.2 +/- 1.8% of the control transfected with wild type OTC cDNA. Clinical features ranged from death during a hyperammonaemic attack (a 9 year old) to a 65 year old asymptomatic man. We consider that the amount of protein ingested by these subjects may be one predisposing factor leading to the manifestation of this disease.
authors.affiliation: Department of Paediatrics, School of Medicine, Kumamoto University, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: T
authors.initials: T
authors.lastname: Matsuura
authors.forename: A
authors.initials: A
authors.lastname: Nishiyori
authors.forename: S
authors.initials: S
authors.lastname: Komaki
authors.forename: R
authors.initials: R
authors.lastname: Hoshide
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: M
authors.initials: M
authors.lastname: Funakoshi
authors.forename: K
authors.initials: K
authors.lastname: Kiwaki
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: A
authors.initials: A
authors.lastname: Hata
authors.forename: M
authors.initials: M
authors.lastname: Shimadzu
authors.forename: M
authors.initials: M
authors.lastname: Yoshino
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000368:Aged; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics*; D000641:Ammonia / Q000097:blood*; D000818:Animals; D019556:COS Cells; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D011379:Prognosis
chemical_list: D000641:Ammonia; D009954:Ornithine Carbamoyltransferase