Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families. (7th February 2013)

• Record Type: Journal Article
• Authors: Storkanova, G; Vlaskova, H; Chuzhanova, N; Zeman, J; Stranecky, V; Majer, F; Peskova, K; Luksan, O; Jirsa, M; Hrebicek, M; Dvorakova, L
• Is Part Of: Clinical genetics. Volume 84:Number 6(2013:Dec.)
• Page Start: 552
• Page End: 559
• Publication Date: 2013-02-07
• Subjects: large deletion -- mutation analysis -- ornithine carbamoyltransferase deficiency -- urea cycle -- X‐inactivation; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12085
• Languages: English
• ISSNs: 0009-9163

Abstract

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.