RESUMO
Steroid 21-hydroxylase deficiency is the underlying cause in over 90% of patients with congenital adrenal hyperplasia, an inherited metabolic disorder of adrenal steroidogenesis. We have characterized 94 mutant alleles from 47 unrelated Mexican patients and the corresponding mutant alleles in their parents by amplification of the functional CYP21 gene by PCR, followed by direct sequence analysis. The study included patients diagnosed with the three clinical forms of the disease. Our results revealed: (1) the presence of relatively few mutations or combinations of mutations associated with particular phenotypes; (2) the presence of putative new mutations; (3) the finding of identical genotypes in patients displaying discordant phenotypes; (4) the identification of patients lacking all previous reported mutations; and (5) an apparent high frequency of germ-line mutations. The absence of previously reported mutations in about 22% of the disease alleles, the finding of putative new mutations in some of the patients lacking previously known mutations, and the apparent high prevalence of germ-line mutations make evident the differences in the genetic background leading to this disorder between the Caucasian and the Mexican populations.
Assuntos
Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/genética , Mutação em Linhagem Germinativa , Mutação Puntual , Esteroide 21-Hidroxilase/genética , Hiperplasia Suprarrenal Congênita/enzimologia , Hiperplasia Suprarrenal Congênita/epidemiologia , Análise Mutacional de DNA , Feminino , Testes Genéticos , Genótipo , Humanos , Masculino , México/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Análise de Sequência de DNARESUMO
To establish a normal range of alpha fetoprotein in maternal serum (AFP sm) in the population at the "20 de Noviembre" Hospital in Mexico City, there were studied 46 patients with a normal pregnancy confirmed with ultrasonography between 16 to 18 week of gestation. The 97 determinations of AFPsm were made by radioimmunoanalysis. The multiples of the median (MoM) were 2.16 al 16th weeks, 2.33 a 17th week 2.43 al 18th week of pregnancy. Now the methods to determine abnormalities in the product and the genetics studies are proposed only to the patients considered high risk (older than 35 years old, previous malformed son or family history of those abnormalities). AFPsm and the establishment of normal range allow us to amplify the study to every pregnant woman and to determine those malformations in the pregnant women of low risk which represents about 90-95% of DCTN and about 80% of SD.