A novel missense mutation in exon 8 of the ornithine transcarbamylase gene in two unrelated male patients with mild ornithine transcarbamylase deficiency
We studied two unrelated male probands with mild ornithine transcarbamylase (OTC) (E.G.188.8.131.52) deficiency presenting a similar clinical course. Previous analyses of their liver OTCs also revealed similar properties. To identify the underlying molecular defects, we first cloned the entire coding region of the OTC gene from one proband and found a single base-substitution (C to T) leading to the substitution of tryptophan for arginine at amino acid position 277. Using a genomic amplification technique followed by allele specific oligonucleotide hybridization, we identified the same point mutation in the OTC gene of the other proband. We observed the presence of the mutation among family members in at least three generations, and in one asymptomatic hemizygous sibling in each family.
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- Adachi T, Tanimura A, Asahina M (1963) A colorimetric determination of orotic acid. J Vitaminol 9:217–226Google Scholar
- Brusilow SW, Horwich AL (1989) Urea cycle enzymes. In: Scriber CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York, pp 629–663Google Scholar
- Brusilow S, Valle D (1987) Allopurinol (AP) induced orotidinuria (ODNU): a test of heterozygosity for ornithine transcarbamylase (OTC) deficiency. Pediatr Res 21:289AGoogle Scholar
- Matsuda I, Nagata N, Oyanagi K, Tsuchiyama A, Yamamoto H, Hase Y, Kodama H, Kai H (1984) Biochemical heterogeneity of ornithine carbamyl transferase (OTC) in patients with OTC deficiency. Jpn J Hum Genet 29:327–333Google Scholar
- Matsuda I, Nagata N, Matsuura T, Oyanagi K, Tada K, Narisawa K, Kitagawa T, Sakiyama T, Yamashita F, Yoshino M (1991) Retrospective survey of urea cycle disorders. I. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase (OTC) deficiency. Am J Med Genet 38:85–89PubMedGoogle Scholar
- Old JM, Briand PL, Purvis-Smith S, Howard NJ, Wilcken B, Hammond J, Pearson P, Cathelineau L, Williamson R, Davies KE (1985) Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis. Lancet I:73–75Google Scholar
- Old JM (1986) Fetal DNA analysis. In: Davies KE (ed) Human genetic diseases: a practical approach. IRL, Oxford Washington, DC, pp 1–17Google Scholar
- Thein SL, Wallace RB (1986) The use of synthetic oligonucleotides as specific hybridization probes in the diagnosis of genetic disorders. In: Davies KE (ed) Human genetic diseases: a practical approach. IRL, Oxford Washington, DC, pp 33–50Google Scholar