Human Genetics

, Volume 97, Issue 2, pp 209–213

Identification of four novel splice site mutations in the ornithine transcarbamylase gene

  • Elisabeth Oppliger Leibundgut
  • Bendicht Wermuth
  • Jean-Pierre Colombo
  • Sabina Liechti-Gallati
Original Investigation

DOI: 10.1007/BF02265267

Cite this article as:
Oppliger Leibundgut, E., Wermuth, B., Colombo, J. et al. Hum Genet (1996) 97: 209. doi:10.1007/BF02265267

Abstract

Ornithine transcarbamylase (OTC) deficiency, the most common inborn error of the urea cycle, shows X-linked inheritance with frequent new mutations. Using polymerase chain reaction (PCR) amplification of the individual exons including adjacent intron sequences followed by direct sequencing of the amplimers we identified four new mutations affecting donor splice sites of introns 2, 5, 6, and 8. The mutation at the first position of intron 2 was a G to A exchange associated with acute neonatal hyperammonemia in a male patient at the age of 5 months. A G to C substitution in intron 5 was detected in a boy who developed 2 days after birth hypotonia, and respiratory distress, followed by severe hyperammonemia and terminal coma. The intron 6 mutation, a G to T substitution, was detected in a girl presenting with first episodes of vomiting and agitation at the age of 2 months. The mutation in intron 8, also a G to T transition, caused fatal hyperammonemia and early death at the age of 15 days in a male patient. We present four donor splice site mutations resulting in severe neonatal or very early onset of the disease in three boys and in one female patient. As the GT dinucleotide of the 5′ donor splice site is invariant and required for correct splicing the described mutations may lead to improperly spliced mRNAs and aberrant gene products.

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Elisabeth Oppliger Leibundgut
    • 1
  • Bendicht Wermuth
    • 1
  • Jean-Pierre Colombo
    • 1
  • Sabina Liechti-Gallati
    • 2
  1. 1.Department of Clinical Chemistry, InselspitalUniversity of BerneBerneSwitzerland
  2. 2.Department of Clinical ResearchUniversity of BerneBerneSwitzerland