MOLECULAR DIAGNOSIS OF SALT WASTING CONGE NITAL ADRENAL-HYPERPLASIA, CAUSED BY DEFICIT OF 21-HYDROXYLASE, IN THE CHILEAN POPULATION

Background: The most frequent cause of congenial adrenal hyperplasia, manifested as virilization and salt wasting, is the deficit of 21-hydr oxylase. This disease is originated by mutations of the gene CYP21 tha t codifies this enzyme, mostly recombination between this gene and its inactive pseudogene called CYP21P. Aim: To study the molecular origin of this enzyme deficiency in Chilean patients. Patients and methods: Twenty five patients with salt wasting congenial adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. I n all patients, a polymerase chain reaction (PCR) with selective prime rs was done with extracted genomic DNA, to amplify the active gene and specific primers for normal or mutated alleles (Allele-specific PCR). Results: The affected allele was identified in 39 (78%) of the 50 chr omosomes of the 25 patients. The higher frequency affected the ASIn2 i n 26% of cases, followed by mutations Arg357Trp in 22% of cases and Gl n319Stop in 12% and deletion in 12%. The identification of two affecte d alleles in a same patient was achieved in 17 cases (68%). The most f requent genotypes were homozygosity for ASIn2 (16%), homozygosity for Arg357Trp (12%) and the homozygote deletion of the gene 12%. Conclusio n: The most frequent mechanisms of genetic damage in this population o f patients with salt wasting congenital adrenal hyperplasia due to def iciency of 21-hydroxylase were the mutations ASIn2 and Arg357Trp. This type of studies allows prenatal diagnosis and genetic counseling.