Abstract
Deficiency of ornithine transcarbamylase (OTC; EC 2.1.3.3), a hepatic mitochondrial enzyme involved in the detoxification of ammonia1,2, is a severe inborn error of metabolism. It is an X-linked disorder2–4 which results characteristically in ammonia intoxication, protein intolerance and mental retardation. Early death of affected hemizygous male infants is common, while clinical manifestations in heterozygous females are variable due to random X-chromosome inactivation2–5. Prenatal diagnosis by amniocentesis has not been feasible because OTC is not expressed in amniocytes and because no unusual metabolites can be detected in amniotic fluid. Fetal liver biopsy has been performed for some families at risk6, but the dangers inherent in this procedure severely limit its usefulness. In this report, we describe the use of a nearly full-length cloned human cDNA7 to begin to characterize normal and mutant human OTC genes. One of 15 affected males was found to have a partial deletion of the OTC gene. Two distinct restriction fragment length polymorphisms (RFLPs) were identified at the OTC locus using the restriction endonuclease MspI; 69% of women tested were heterozygous for one or both polymorphisms. Identification of these common polymorphisms makes it possible to offer prenatal diagnosis to a large fraction of obligate carriers and to provide information on carrier status to some females at risk.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Grisolia, S., Baguena, R. & Mayor, F. (eds) The Urea Cycle (Wiley, New York, 1976).
Walser, M. in The Metabolic Basis of Inherited Disease (eds Stanbury, J. B., Wyngaarden, J. B., Fredrickson, D. S., Goldstein, J. L. & Brown, M. S.) 402–419 (McGraw-Hill, New York, 1983).
Short, E. M., Conn, H. O., Snodgrass, P. J., Campbell, A. G. M. & Rosenberg, L. E. New Engl. J. Med. 288, 7–12 (1973).
Ricciuti, F. C., Gelehrter, T. D. & Rosenberg, L. E. Am. J. hum. Genet. 28, 332–338 (1976).
Rosenberg, L. E. & Scriver, C. R. in Metabolic Control and Disease (eds Bondy, P. K. & Rosenberg, L. E.) 682–687 (Saunders, Philadelphia, 1980).
Rodeck, C. H., Pembrey, M. E., Patrick, A. D. & Tzannatos, C. Lancet ii, 297–300 (1982).
Horwich, A. L. et al. Science 224, 1068–1074 (1984).
Haldane, J. B. S. J. Genet. 31, 317–326 (1935).
Orkin, S. H. & Nathan, D. G. in Advances in Human Genetics (eds Harris, H. & Hirschhorn, K.) 233–280 (Plenum, New York, 1981).
Botstein, D., White, R. L., Skolnick, M. & Davis, R. W. Am. J. hum. Genet. 32, 314–331 (1980).
Batshaw, M. L., Roan, Y., Jung, A. L., Rosenberg, L. A. & Brusilow, S. W. New. Engl. J. Med. 302, 482–485 (1980).
Geever, R. F. et al. Proc. natn. Acad. Sci. U.S.A. 78, 5081–5085 (1981).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Rigby, P. W. J., Dieckmann, M., Rhodes, C. & Berg, P. J. J. molec. Biol. 113, 237–254 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rozen, R., Fox, J., Fenton, W. et al. Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus. Nature 313, 815–817 (1985). https://doi.org/10.1038/313815a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313815a0
This article is cited by
-
Validation of mRNA/EST-based gene predictions in human Xp11.4 revealed differences to the organization of the orthologous mouse locus
Mammalian Genome (2005)
-
Identification of four novel splice site mutations in the ornithine transcarbamylase gene
Human Genetics (1996)
-
Identification of two new aberrant splicings in the ornithine carbamoyltransferase (OCT) gene in two patients with early and late onset OCT deficiency
Journal of Inherited Metabolic Disease (1995)
-
Human methylenetetrahydrofolate reductase: isolation of cDNA, mapping and mutation identification
Nature Genetics (1994)
-
Specificity of PCR‐SSCP for detection of the mutant ornithine transcarbamylase (OTC) gene in patients with OTC deficiency
Journal of Inherited Metabolic Disease (1993)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.