Human Genetics

, Volume 88, Issue 2, pp 153–156

Fatal hyperammonemia resulting from a C-to-T mutation at a MspI site of the ornithine transcarbamylase gene

Authors

  • Danièle Hentzen
    • Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12 et Laboratoire de Biochimie, Hôpital des Enfants-Malades
  • Anna Pelet
    • Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12 et Laboratoire de Biochimie, Hôpital des Enfants-Malades
  • Delphine Feldman
    • Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12 et Laboratoire de Biochimie, Hôpital des Enfants-Malades
  • Daniel Rabier
    • Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12 et Laboratoire de Biochimie, Hôpital des Enfants-Malades
  • Jacques Berthelot
    • Service de Pédiatrie Génétique, Centre Hospitalier Universitaire
  • Arnold Munnich
    • Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-12 et Laboratoire de Biochimie, Hôpital des Enfants-Malades
Original Investigations

DOI: 10.1007/BF00206063

Cite this article as:
Hentzen, D., Pelet, A., Feldman, D. et al. Hum Genet (1991) 88: 153. doi:10.1007/BF00206063

Summary

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle in humans and is responsible for lethal neonatal hyperammonemia in males. Partial OTC deficiency also occurs in females and can be responsible for life-threatening hyperammonemic comas in heterozygotes. The cosegregation of the trait with a 5.8-kb abnormal MspI fragment in an affected family led us to hypothesize that this unexpected migration pattern was related to the mutation event in this particular family. Using polymerase chain reaction amplification of the specific mRNA derived from a post-mortem biopsy of the liver, we found that the MspI site located in the seventh exon of the gene was abolished and we finally identified a C-to-T transition at codon 225 of the cDNA, changing a proline to a leucine in the protein. Subsequent digestion of amplified exon 7 using the restriction enzyme MspI allowed direct screening for the mutant genotype during the next pregnancy. The present study supports the view that direct detection of the mutant genotype using either Southern blotting or digestion of amplified exons of the gene can contribute to genetic counselling in non-informative families. Finally, since MspI digestions are routinely performed for restriction fragment length polymorphism-based family studies in OTC deficiency, we suggest that the possible presence of the 5.8-kb abnormal fragment should be investigated on Southern blots of affected individuals.

Copyright information

© Springer-Verlag 1991