[Molecular diagnosis of salt wasting congenital adrenal hyperplasia, caused by deficit of 21-hydroxylase, in the Chilean population].
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.


OBJECTIVE
To study the molecular origin of this enzyme deficiency in Chilean patients.


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%.


CONCLUSIONS
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.
Pineda
P
P
Departamento de Endocrinología, Pontificia Universidad Católica de Chile, Santiago.
Fardella
C
C
Poggi
H
H
Torrealba
I
I
Cattani
A
A
Soto
J
J
Foradori
A
A
D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D002677:Chile; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
Diagnóstico molecular de hiperplasia suprarrenal congénita por déficit de 21-hidroxilasa, variedad perdedora de sal, en población chilena.