Abstract
OTC, the second enzyme of the urea cycle, is a mitochondrial protein encoded on the X chromosome. Inherited OTC deficiency, which typically leads to neonatal ammonia intoxication and early death in hemizygous affected males, cannot currently be detected prenatally by amniocentesis because OTC is not expressed in amniocytes. To develop such diagnostic capability by examining directly the OTC gene, a rat OTC cDNA was used to screen a human liver cDNA library. Several clones containing human OTC sequences were isolated. A plasmid was constructed containing the entire human OTC coding sequence (1500 bp), and was used as probe in Southern blot analysis of DNA prepared from control human cells and from cultured fibroblasts of 7 patients with lethal OTC deficiency. Studies with Eco RI and several other restriction enzymes indicated that the human OTC gene normally spans 30 kb and contains at least 8 introns. Blots from 6 of 7 OTC-deficient patients were indistinguishable from controls. In the 7th, however, whose liver contained no detectable OTC activity or cross-reacting material, restriction with Eco RI or Hind III revealed the absence of a 3.0-3.5 kb band; no new bands were seen. This OTC gene deletion was localized to the 3' end of the OTC coding sequence. Furthermore, we have observed an RFLP, using Msp I, in 2 of 10 female controls, and are searching for other RFLPs which may be useful in counselling those families at risk whose genetic defect does not involve gene deletion.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rozen, R., Horwich, A., Fenton, W. et al. GENE DELETION AND RESTRICTION FRAGMENT LENGTH POLYMORPHISM (RFLP) AT THE HUMAN ORNITHINE TRANSCARBAMYLASE (OTC) LOCUS. Pediatr Res 18 (Suppl 4), 225 (1984). https://doi.org/10.1203/00006450-198404001-00791
Issue Date:
DOI: https://doi.org/10.1203/00006450-198404001-00791