Get access

Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families

Authors

  • G Storkanova,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
    • These authors contributed equally to the manuscript.

  • H Vlaskova,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
    • These authors contributed equally to the manuscript.

  • N Chuzhanova,

    1. School of Science and Technology, Nottingham Trent University, Nottingham, UK
    Search for more papers by this author
  • J Zeman,

    1. Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
  • V Stranecky,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
  • F Majer,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
  • K Peskova,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
  • O Luksan,

    1. Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
    Search for more papers by this author
  • M Jirsa,

    1. Laboratory of Experimental Hepatology, Institute for Clinical and Experimental Medicine (IKEM), Prague, Czech Republic
    Search for more papers by this author
  • M Hrebicek,

    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    Search for more papers by this author
  • L Dvorakova

    Corresponding author
    1. Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic
    • Corresponding author: Lenka Dvorakova, Institute of Inherited Metabolic Disorders, Laboratory of DNA diagnostics, bldg E1A, Ke Karlovu 2, Prague 2, 128 08, Czech Republic.

      Tel.: +420 224 967 701;

      fax: +420 224 967 168;

      e-mail: lenka.dvorakova@lf1.cuni.cz

    Search for more papers by this author

  • The authors declare that they have no conflict of interest.

Abstract

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.

Ancillary