Substitution in the promoter region ofthe CYP21 affects a phenotype ofthe disease in patients with 21-hydroxylase deficiency
Abstract
In family report there is presented the case of the six-year-old boy, who was being observed for the manifestation of praecox pubarche and for excessive growth of the figure. His clinical symptomts corresponded to the simple virilizing form of congenital adrenal hyperplasia.
To confirm the given diagnose the patient was examined by the molecular genetic analysis of deficit 21-hydroxylase. After the basic DNA analysis the genotype of the boy was determined as the compound heterozygote carrying the chimeric CYP21P/CYP21 gene on the paternal allele and an unknown mutation on the maternal allele.
Using the MLPA method and sequencing method of the CYP21 gene we defined atypical mutant allele with a large gene conversion on maternal allele (5'- untranslated region including the promotor and sequence of the 1. exon in the CYP21 gene). It was described that this type of allele significantly decreases the activity of the enzyme 21-hydroxylase enzyme (to 4-10 %), which results in the manifestation of more difficult form of CAH disease, mostly SV form.