{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T22:11:21Z","timestamp":1760739081175,"version":"build-2065373602"},"reference-count":17,"publisher":"BMJ","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,8]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1136\/jmg.33.8.645","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"645-648","source":"Crossref","is-referenced-by-count":25,"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."],"prefix":"10.1136","volume":"33","author":[{"given":"I","family":"Matsuda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Matsuura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Nishiyori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Komaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R","family":"Hoshide","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Funakoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K","family":"Kiwaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Endo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Hata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Shimadzu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1996,8,1]]},"reference":[{"key":"ref_1","first-page":"1187","article-title":"Urea cycle enzymes","volume-title":"The metabolic and molecular basis of inherited disease","author":"Brusilow, S.W.; Horwich, A.L.","year":"1995","unstructured":"Brusilow SW, Horwich AL. Urea cycle enzymes. In: Scriber CR, Beaudet AL, Sly WS, Valle D, eds. The metabolic and molecular basis of inherited disease. 7th ed. New York: McGraw-Hill, 1995:1187-232.","edition":"7th ed"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1126\/science.6372096","article-title":"Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase","volume":"224","author":"Horwich, A.L.; Fenton, W.A.; Williams, K.","year":"1984","unstructured":"Horwich AL, Fenton WA, Williams K, et al. Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase. Science 1984;224: 1068-74.","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1093\/oxfordjournals.jbchem.a122265","article-title":"Structure of the human ornithine transcarbamylase gene","volume":"103","author":"Hata, A.; Tsuzuki, T.; Shimada, K.; Takiguchi, M.; Mori, M.; Matsuda, I.","year":"1988","unstructured":"Hata A, Tsuzuki T, Shimada K, Takiguchi M, Mori M, Matsuda I. Structure of the human ornithine transcarbamylase gene. J Biochem 1988;103:302-8.","journal-title":"J Biochem"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/ajmg.1320380119","article-title":"Retrospective survey of urea cycle disorders. Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency","volume":"38","author":"Matsuda, I.; Nagata, N.; Oyanagi, K.","year":"1991","unstructured":"Matsuda I, Nagata N, Oyanagi K, et al. Retrospective survey of urea cycle disorders. Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency. Am J Med Genet 1991;38:85-9.","journal-title":"Am J Med Genet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1002\/ajmg.1320400421","article-title":"Retrospective survey of urea cycle disorders. Part 2. Neurological outcome in forty-nine Japanese patients with urea cycle enzymopathies","volume":"40","author":"Nagata, N.; Matsuda, I.; Matsuura, T.","year":"1991","unstructured":"Nagata N, Matsuda I, Matsuura T, et al. Retrospective survey of urea cycle disorders. Part 2. Neurological outcome in forty-nine Japanese patients with urea cycle enzymopathies. 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Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency; application of PCR-single standard conformation polymorphism for all exons and adjacent introns. Hum Genet 1993;92:49-56.","journal-title":"Hum Genet; adjacent introns"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1002\/humu.1380040109","article-title":"Seven new mutations in the human ornithine transcarbamylase gene","volume":"4","author":"Tuchman, M.; Plante, R.J.; McCann, M.T.; Qureshi, A.A.","year":"1994","unstructured":"Tuchman M, Plante RJ, McCann MT, Qureshi AA. Seven new mutations in the human ornithine transcarbamylase gene. 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Ornithine transcarbamylase deficiency in male adolescence and adulthood. Enzyme 1990;43:160-8.","journal-title":"Enzyme"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/BF00711312","article-title":"Prenatal monitoring of ornithine transcarbamylase deficiency in two families by DNA analysis","volume":"16","author":"Matsuura, T.; Hoshide, R.; Fukushima, M.; Sakiyama, T.; Owada, M.; Matsuda, I.","year":"1993","unstructured":"Matsuura T, Hoshide R, Fukushima M, Sakiyama T, Owada M, Matsuda I. Prenatal monitoring of ornithine transcarbamylase deficiency in two families by DNA analysis. Jf Inherited Metab Dis 1993;16:31-8.","journal-title":"Jf Inherited Metab Dis"},{"key":"ref_12","first-page":"129","article-title":"Expression of four mutant human ornithine transcarbamylase genes in cultured COS-1 cells relates to clinical phenotypes","volume":"93","author":"Matsuura, T.; Hoshide, R.; Setoyama, C.","year":"1994","unstructured":"Matsuura T, Hoshide R, Setoyama C, et al. Expression of four mutant human ornithine transcarbamylase genes in cultured COS-1 cells relates to clinical phenotypes. Hum Genet 1994;93:129-34.","journal-title":"Hum Genet"},{"key":"ref_13","first-page":"283","article-title":"Structure of ornithine transcarbamylase (OTC) gene and DNA diagnosis of OTC deficiency","volume":"85","author":"Matsuda, I.; Hata, A.; Matsuura, T.; Tsuzuki, T.; Shimada, K.","year":"1989","unstructured":"Matsuda I, Hata A, Matsuura T, Tsuzuki T, Shimada K. Structure of ornithine transcarbamylase (OTC) gene and DNA diagnosis of OTC deficiency. Clin Chim Acta 1989; 85:283-90.","journal-title":"Clin Chim Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/j.1432-1033.1987.tb13525.x","article-title":"Nucleotide sequence of ARG 3 gene of the yeast Saccharomyces cerevisiae encoding ornithine carbamyltransferase. Comparison with other carbamyltransferases","volume":"166","author":"Huygen, R.; Crafeel, M.; Glansdorff, N.","year":"1987","unstructured":"Huygen R, Crafeel M, Glansdorff N. Nucleotide sequence of ARG 3 gene of the yeast Saccharomyces cerevisiae encoding ornithine carbamyltransferase. Comparison with other carbamyltransferases. EurJ Biochem 1987;166:371-7.","journal-title":"EurJ Biochem"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1136\/bmj.292.6512.23","article-title":"Evidence of inherited urea cycle defect in a case of fetal valproate toxicity","volume":"292","author":"Hjelm, M.; DeSilva, L.V.K.; Seakins, J.W.T.","year":"1986","unstructured":"Hjelm M, DeSilva LVK, Seakins JWT. Evidence of inherited urea cycle defect in a case of fetal valproate toxicity. BMJ 1986;292:23-4.","journal-title":"BMJ"},{"key":"ref_16","first-page":"1283","article-title":"Valproate toxicity and ornithine transcarbamylase deficiency","volume":"ii:","author":"Kay, J.P.S.; Hilton-Jones, D.; Hyman, N.","year":"1986","unstructured":"Kay JPS, Hilton-Jones D, Hyman N. Valproate toxicity and ornithine transcarbamylase deficiency. Lancet 1986; ii: 1283-4.","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/BF01213087","article-title":"A novel mutation in exon 8 of the ornithine transcarbamylase gene in two unrelated male patients with mild ornithine transcarbamylase deficiency","volume":"87","author":"Hata, A.; Matsuura, T.; Setoyama, C.","year":"1991","unstructured":"Hata A, Matsuura T, Setoyama C, et al. A novel mutation in exon 8 of the ornithine transcarbamylase gene in two unrelated male patients with mild ornithine transcarbamylase deficiency. 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