Analysis of steroid 21-hydroxylase gene mutations in the Spanish population

Abstract

Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia. Genotyping for deletions and nine point mutations in the CYP21 gene has been performed in 38 Spanish patients and their relatives by Southern blot analysis and allele-specific oligonucleotide hybridization. Three clinical variants were included in this study, viz., salt-wasting (SW, 21 patients), simple virilizer (SV, two patients), and late-onset (LO, 15 patients) forms. Twenty-three patient genotypes (16 SW, two SV, and five LO) were fully characterized. In both alleles, all but one of these severe forms (SW and SV) presented mutations that abolished or severely affected enzymatic activity. Patients with LO forms showed mutations that moderately impaired enzymatic activity in both alleles, or severe mutations in only one chromosome. Of 46 chromosomes from severe forms, 41 were characterized in this study (89%). The most frequent mutation was an aberrant splicing site (655 A or C to G) in intron 2, in 30% of these chromosomes. Deletions were found in 20%, and large gene conversions in 13% of these alleles. This screening allowed the characterization of 18 out of 30 LO chromosomes, the most frequent mutation being Val281Leu (37%). Severe mutations were found, in heterozygosis, in one third of LO patients.

21-Hydroxylase deficiency in Brazil

“…The most frequent mutations in our series were those also present in the pseudogene, similarly to previous reports (12,14,20,24,25), except for the Del 8nt mutation, which is normally associated with the classical form and was detected only in heterozygosis in the LO form. Studies involving approximately 10 mutations, comprising large and point mutations, diagnosed 77.6 to 95% of the alleles (12,14,17,25). Even though we screened for 17 mutations, we had a significant number of unidentified alleles (20%).…”

“…Since rare mutations were also scarcely found or even absent in our alleles, we suppose that new mutations might be present in our population, as observed in a Mexican study (21). The highest frequency of undiagnosed alleles in our series was found in the LO form, as well as in other large series (14,25). However, we did not rule out the presence of other rare mutations such as P105L, R339H or promoter mutations that have been found in the LO form (26).…”

CYP21 and CYP21P variability in steroid 21-hydroxylase deficiency patients and in the general population in the Netherlands

“…They vary among different populations. 8,17,18,22,[26][27][28][29][30][31][32][33][34][35][36][37] However, information on the variability of the CYP21P pseudogene, especially in association with the TaqI/BglII haplotypes that define the overall structure of the region, is rather limited. 18,38 Such information is highly relevant to the hypotheses describing the origin of the different categories of disease-causing mutations in CYP21: the location of crossover sites and the extent of conversion zones depend on the composition of the CYP21P gene involved.…”

The Prevalence of Non-classical Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Greek Women with Hirsutism and Polycystic Ovary Syndrome

“…As previously reported, the prevalence of 21-OHdef varies from 1% to 20%-30% and it is particularly high around the Mediterranean, in Italians, in the Jewish Ashkenazi, in the Hispanics, in the Turks and in the Arabs [34][35][36][37][38]. Recently published papers in Turkey, reported a high prevalence of NC-CAH due to 21-OHdef in women suffering from hirsutism and PCOS [11,34,35].…”