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Mutational Spectrum and Linkage Disequilibrium Patterns at the Ornithine Transcarbamylase Gene ( OTC )
Author(s) -
Azevedo L.,
Soares P. A.,
Quental R.,
Vilarinho L.,
Teles E. L.,
Martins E.,
Diogo L.,
Garcia P.,
Cenni B.,
Wermuth B.,
Amorim A.
Publication year - 2006
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2006.00283.x
Subject(s) - ornithine transcarbamylase , ornithine transcarbamylase deficiency , genetics , ornithine carbamoyltransferase , exon , biology , urea cycle , point mutation , gene , mutation , microbiology and biotechnology , ornithine , arginine , amino acid
Summary 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.