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2996371 
Journal Article 
Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families 
Storkanova, G; Vlaskova, H; Chuzhanova, N; Zeman, J; Stranecky, V; Majer, F; Peskova, K; Luksan, O; Jirsa, M; Hrebicek, M; Dvorakova, L 
2013 
Yes 
Clinical Genetics
ISSN: 0009-9163
EISSN: 1399-0004 
84 
6 
552-559 
English 
23278509 
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.