Molecular genotyping in Brazilian patients with the classical and nonclassical forms of 21-hydroxylase deficiency

The aim of our study was to determine, by allele-specific PGR, the frequenc y of point mutations in 130 Brazilian patients with the classical and noncl assical forms of 21-hydroxylase deficiency and to correlate genotype with p henotype. 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 re ported for other countries, except for Del 8 nt and Cluster, which were les s frequent in the classical form. Rarer mutations such as P453S, G291S, 17 splice, W405X, R483P, and R483-->frameshift were rarely found or were absen t. The 93 fully genotyped patients were classified into 3 mutation groups, based on the degree of enzymatic activity (group A, <2%; group B, similar t o 2%, and group C, >18%). In group A, 62% of the cases presented the salt w asting 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 scree ning for large rearrangements and 15 point mutations. The absence of previo usly described mutations in 20% of the affected alleles suggests the presen ce of new mutations in our population.