Abstract
We have utilized the Southern blotting technique to analyse genomic DNA from males with ornithine transcarbamylase (OTC) deficiency and their families. Using a nearly full-length human cDNA probe, we have identified 3 patients with deletions at this locus and have characterized 4 different restriction fragment length polymorphisms that can be used as linkage markers for the OTC mutation. These polymorphisms occur at sufficiently high frequencies so as to enable us to distinguish the two X-chromosomes in approximately 80% of OTC carriers. As a direct consequence of these findings, prenatal diagnosis and carrier assessment can be offered to a large fraction of families at risk for OTC deficiency.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Brusilow, S. W., Danney, M., Waber, L. J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C. and Ward J. Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.N. Engl. J. Med. 310 (1984) 1630–1634
Brusilow, S. W. and Valle, D. L. Identification of heterozygosity for ornithine transcarbamylase deficiency (OTCD).Pediatr. Res. 19 (1985) 244A
Davies, K. E., Pearson, P. L., Harper, P. S., Murray, J. M., O'Brien, T. and Williamson, R. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X-chromosome.Nucleic Acids Res. 11 (1983) 2303–2312
Francke, U., Ochs, H. D., de Martinville, B., Giacalone, J., Lindgren, V., Distèche, C., Pagon, R., Hofker, M. H., van Ommen, G-J. B., Pearson, P. L. and Wedgwood, R. J. Minor Xp21 chromosome deletion in a male associated with expression of Duchenne muscular dystrophy, chronic granulomatous disease, retinitis pigmentosa and McLeod syndrome.Am. J. Hum. Genet. 37 (1985) 250–267
Grisolia, S., Baguena, R. and Mayor, F. (eds.)The Urea Cycle, Wiley, New York, 1976
Haldane, J. B. S. Rate of spontaneous mutation of the human gene.J. Genet. 31 (1935) 317–326
Hofker, M. H., Wapenaar, M., Goor, N., Bakker, E., van Ommen, G-J. B. and Pearson, P. L. Isolation of probes detecting restriction fragment length polymorphisms from chromosome specific libraries: potential use for diagnosis of Duchenne muscular dystrophy.Hum. Genet. 70 (1985) 148–156
Holzgreve, W. and Golbus, M. S. Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy.Am. J. Hum. Genet. 36 (1984) 320–328
Horwich, A. L., Fenton, W. A., Williams, K. R., Kalousek, F., Kraus, J. P., Doolittle, R. F., Konigsberg, W. and Rosenberg, L. E. Structure and expression of a complementary DNA for the nuclear coded precursor of human mitochondrial ornithine transcarbamylase.Science 224 (1984) 1068–1074
Lindgren, V., de Martinville, B., Horwich, A. L., Rosenberg, L. E. and Francke, U. Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus.Science 226 (1984) 698–700
Ricciuti, F. C., Gelehrter, T. D. and Rosenberg, L. E. X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase.Am. J. Hum. Genet. 28 (1976) 332–338
Rodeck, C. H., Patrick, A. D., Pembrey, M. E., Tzannatos, C. and Whitfield, A. E. Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency.Lancet 1 (1982) 297–299
Rozen, R., Fox, J., Fenton, W. A., Horwich, A. L. and Rosenberg, L. E. Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.Nature 313 (1985) 815–817
Short, E. M., Conn, H. O., Snodgrass, P. J., Campbell, A. G. M. and Rosenberg, L. E. Evidence for X-linked dominant inheritance of ornithine transcarbamylase deficiency.N. Engl. J. Med. 288 (1973) 7–12
Walser, M. Urea cycle disorders and other hereditary hyperammonemic syndromes. In Stanbury, J. B., Wyngaarden, J. B., Frederickson, D. S., Goldstein, J. L. and Brown, M. S. (eds.)The Metabolic Basis of Inherited Disease, 5th edn. McGraw-Hill, New York, 1983, pp. 402–438
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rozen, R., Fox, J.E., Hack, A.M. et al. DNA analysis for ornithine transcarbamylase deficiency. J Inherit Metab Dis 9 (Suppl 1), 49–57 (1986). https://doi.org/10.1007/BF01800858
Issue Date:
DOI: https://doi.org/10.1007/BF01800858