These authors contributed equally to the manuscript.
Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families
Article first published online: 7 FEB 2013
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 84, Issue 6, pages 552–559, December 2013
How to Cite
Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families., , , , , , , , , , .
The authors declare that they have no conflict of interest.
- Issue published online: 28 OCT 2013
- Article first published online: 7 FEB 2013
- Accepted manuscript online: 26 DEC 2012 12:48PM EST
- Manuscript Revised: 21 DEC 2012
- Manuscript Accepted: 21 DEC 2012
- Manuscript Received: 9 OCT 2012
- MZCR project. Grant Number: 00023001
- large deletion;
- mutation analysis;
- ornithine carbamoyltransferase deficiency;
- urea cycle;
Ornithine carbamoyltransferase deficiency is the most common inherited defect of the urea cycle. We examined 28 male and 9 female patients from 29 families and identified 25 distinct mutations in OTC, 14 of which were novel. Three novel missense mutations (p.Ala102Pro, p.Pro158Ser, p.Lys210Glu) and a novel deletion of the Leu43 are not directly involved either in the enzyme active site or in the intersubunit interactions; however, the mutations include conserved residues involved in intramolecular interaction network essential for the function of the enzyme. Three novel large deletions – a 444 kb deletion affecting RPGR, OTC and TSPAN7, a 10 kb-deletion encompassing OTC exons 5 and 6 and a 24.5 kb-deletion encompassing OTC exons 9 and 10 – have probably been initiated by double strand breaks at recombination-promoting motifs with subsequent non-homologous end joining repair. Finally, we present a manifesting heterozygote carrying a hypomorphic mutation p.Arg129His in combination with unfavorably skewed X-inactivation in three peripheral tissues.