title: Molecular genotyping in Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency.
abstract: The aim of our study was to determine, by allele-specific PCR, the frequency of point mutations in 130 Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency and to correlate genotype with phenotype. The most frequent mutations were 12 splice (41.8% in salt wasting), I172N (32.6% in simple virilizing), and V281L (40.2% in late onset form). The frequency of the 9 most common point mutations was similar to that reported for other countries, except for Del 8 nt and Cluster, which were less frequent in the classical form. Rarer mutations such as P453S, G291S, I7 splice, W405X, R483P, and R483-->frameshift were rarely found or were absent. The 93 fully genotyped patients were classified into 3 mutation groups, based on the degree of enzymatic activity (group A, <2%; group B, approximately 2%, and group C, >18%). In group A, 62% of the cases presented the salt wasting form; in group B, 96% the simple virilizing form; and in group C, 88% the late onset form. We diagnosed 80% of the affected alleles after screening for large rearrangements and 15 point mutations. The absence of previously described mutations in 20% of the affected alleles suggests the presence of new mutations in our population.
authors.affiliation: Unidade de Endocrinologia do Desenvolvimento, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, Brazil.
authors.forename: T A
authors.initials: TA
authors.lastname: Bachega
authors.forename: A E
authors.initials: AE
authors.lastname: Billerbeck
authors.forename: G
authors.initials: G
authors.lastname: Madureira
authors.forename: J A
authors.initials: JA
authors.lastname: Marcondes
authors.forename: C A
authors.initials: CA
authors.lastname: Longui
authors.forename: M V
authors.initials: MV
authors.lastname: Leite
authors.forename: I J
authors.initials: IJ
authors.lastname: Arnhold
authors.forename: B B
authors.initials: BB
authors.lastname: Mendonca
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000235:genetics; D000483:Alleles; D001938:Brazil; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D013255:Steroid 21-Hydroxylase / Q000235:genetics
chemical_list: D013255:Steroid 21-Hydroxylase