title: Ornithine carbamoyltransferase deficiency: molecular characterization of 29 families.
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.
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague, and General University Hospital in Prague, Czech Republic.
authors.forename: G
authors.initials: G
authors.lastname: Storkanova
authors.forename: H
authors.initials: H
authors.lastname: Vlaskova
authors.forename: N
authors.initials: N
authors.lastname: Chuzhanova
authors.forename: J
authors.initials: J
authors.lastname: Zeman
authors.forename: V
authors.initials: V
authors.lastname: Stranecky
authors.forename: F
authors.initials: F
authors.lastname: Majer
authors.forename: K
authors.initials: K
authors.lastname: Peskova
authors.forename: O
authors.initials: O
authors.lastname: Luksan
authors.forename: M
authors.initials: M
authors.lastname: Jirsa
authors.forename: M
authors.initials: M
authors.lastname: Hrebicek
authors.forename: L
authors.initials: L
authors.lastname: Dvorakova
mesh_terms: D000293:Adolescent; D000483:Alleles; D000641:Ammonia / Q000097:blood; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D023061:Gene Order; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000175:diagnosis* / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D000641:Ammonia; D009954:Ornithine Carbamoyltransferase
keywords: X-inactivation; large deletion; mutation analysis; ornithine carbamoyltransferase deficiency; urea cycle