title: Mutational spectrum and linkage disequilibrium patterns at the ornithine transcarbamylase gene (OTC).
abstract: Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a hepatic enzyme involved in ammonia elimination via the urea cycle. Since the sequence of the OTC gene was reported many types of mutations continue to be found in OTC deficiency patients, continuing to increase the already wide mutational spectrum known for this gene. In this study we present the clinical, biochemical and molecular features of thirteen late-onset OTC deficiency patients. Mutations were identified in all these patients, among which six were novel point substitutions (L59R, A137P, L148S, Y176L, L186P, and K210N) and one was a 2-bp deletion at exon 4 (341-342delAA). In addition, a de novo genomic deletion of maternal origin encompassing exons 1 to 5 was also identified by the analysis of LD patterns using intragenic polymorphic markers. This work exemplifies the potential value of population genetic studies for the detection of large deletions.
authors.affiliation: Institute of Pathology and Molecular Immunology, University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal. luisa.azevedo@ipatimup.pt
authors.forename: L
authors.initials: L
authors.lastname: Azevedo
authors.forename: P A
authors.initials: PA
authors.lastname: Soares
authors.forename: R
authors.initials: R
authors.lastname: Quental
authors.forename: L
authors.initials: L
authors.lastname: Vilarinho
authors.forename: E L
authors.initials: EL
authors.lastname: Teles
authors.forename: E
authors.initials: E
authors.lastname: Martins
authors.forename: L
authors.initials: L
authors.lastname: Diogo
authors.forename: P
authors.initials: P
authors.lastname: Garcia
authors.forename: B
authors.initials: B
authors.lastname: Cenni
authors.forename: B
authors.initials: B
authors.lastname: Wermuth
authors.forename: A
authors.initials: A
authors.lastname: Amorim
mesh_terms: D005091:Exons; D005260:Female; D005819:Genetic Markers; D005828:Genetics, Population; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D009954:Ornithine Carbamoyltransferase / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D009954:Ornithine Carbamoyltransferase