Estudo molecular da hiperplasia adrenal congenita por deficiencia da enzima 21-hidroxilase correlação genotipo-fenotipo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH-21OHD) is one of the most common inborn metabolism errors. It presents a wide spectrum of clinical manifestations, varying from a severe form with prenatal virilization and neonatal dehydration to a mild form in which the signs appear around puberty onset. It presents recessive autosomal inheritance and occurs due to mutations in the CYP21 gene, which codifies the 21-hydroxylase enzyme. Mutations leading to less enzymatic activity are related to the classical form and those with more enzymatic activity with nonclassical form of the disease. We studied the frequency of the 7 most frequent point mutations reported in CYP21 gene in 50 families with CAH-21OHD, 21 with classic salt wasting patients (SW), 17 with classic simple virilizing patients (SV) and 13 with nonclassic form (NC). In addition, we correlated the phenotype with the genotype observed in all patients studied. We used genomic DNA to amplify CYP21 gene by allele-specific PCR. Mutations had been identified in 93 alleles. The more frequent mutation found was I172N (21.5%) followed by V281L (18.2%), IVS2, A/C>G,-12 (Sp2) (14.0%) and R356W (6.5%), Q318X (1.1%) and P30L (1.1%) and 706_713del8 (D8) (1.1%). The genotype was divided in groups A, B and C, in an increasing order of enzymatic activity. These three groups were compared to the SW, SV and NC forms, respectively. There was a strong correlation of phenotype with the genotype (100% for C group, 100% for B group and 88.8% for A group). In conclusion, the frequency of microconversions found in this study was similar to those observed in the worldwide and in a Brazilian sub population

ASSUNTO(S)

mutação (biologia) hiperplasia

ACESSO AO ARTIGO

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