Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.

摘要: Ornithine transcarbamylase (OTC) deficiency, a partially dominant X-linked disorder, is the most common inherited defect of urea cycle. Previous reports suggested variable phenotypic spectrum, and several studies documented different "private" mutations in OTC genes patients. Our laboratory identified disease-causing 157 families with 100 which came to medical attention through hemizygous propositus 57 index case was heterozygous female. We correlated genotype age onset, liver activity, incorporation nitrogen into urea, peak plasma ammonia levels. The "neonatal onset" group has homogeneous clinical biochemical phenotype, whereas "late shows an extremely wide phenotype; 60% are associated exclusively acute neonatal hyperammonemic coma. remaining caused nonuniform phenotype ranging from severe disease no symptoms; 31% gene occur CpG dinucleotides (methylation-mediated deamination), none them accounted for more than 4% total. Eighty-six percent represented single-base substitutions 68% were transitions. G-to-A C-to-T transitions frequent (34 21%, respectively) C-to-A, A-to-C, C-to-G, T-to-A transversions least (1.5-3%). Twenty propositi 77% propositae carried new mutations. Forty female germinal this number appears much smaller male These data allow classification patients deficiency at two groups who have discordant course prognoses. In addition, they improve our understanding on origin better counseling affected families.