[Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population]. / Diagnóstico molecular de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa, variedad perdedora de sal, en población chilena.

ABSTRACT

BACKGROUND: The most frequent cause of congenital adrenal hyperplasia, manifested as virilization and salt wasting, is the deficit of 21-hydroxylase. This disease is originated by mutations of the gene CYP21 that 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 congenital adrenal hyperplasia, that had 17-hydroxyprogesterone levels above 30 ng/ml, were studied. In all patients, a polymerase chain reaction (PCR) with selective primers 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 chromosomes of the 25 patients. The higher frequency affected the ASIn2 in 26% of cases, followed by mutations Arg357Trp in 22% of cases and Gln319Stop in 12% and deletion in 12%. The identification of two affected alleles in a same patient was achieved in 17 cases (68%). The most frequent genotypes were homozygosity for ASIn2 (16%), homozygosity for Arg357Trp (12%) and the homozygote deletion of the gene in 12%. CONCLUSION: The most frequent mechanisms of genetic damage in this population of patients with salt wasting congenital adrenal hyperplasia due to deficiency of 21-hydroxylase were the mutations ASIn2 and Arg357Trp. This type of studies allows prenatal diagnosis and genetic counseling.