CYP21 gene mutations in Brazilian patients with 21-hydroxylase deficiency from the Amazon region

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (P450c21, CYP21) accounts for about 95% of all CAH cases. The incidence of CYP21 gene mutations has been extensively studied in the last years, but in Brazil it has been investigated only in Southeast Brazilian patients. This study is the first report on the distribution of CYP21 mutations in patients from the Amazon region. Direct sequencing of the CYP21 gene identified at least one mutation in 96% of the studied chromosomes. The most common mutations found were IVS2-13A/C > G (36%), Q318X (12%), V281L (12%), 1760_1761insT (9%), Cluster E6 (7%), and P30L (7%). The worldwide most common mutations were identified among patients from the Amazon region at frequencies that may be expected for a population resulting from the admixture of Europeans (predominantly Portuguese), African Blacks and Amerindians, in proportions that differ from those estimated for South Brazilian populations. Interethnic mixture may explain the differences in the frequencies of some mutations between Brazilian patients from the Amazon and from the Southeast of the country. However, the differences found may also be due to variation in the number of patients with the different clinical forms of 21-hydroxylase deficiency in the studies carried out so far.

Genotype-Phenotype Correlation in CAH Patients with Severe CYP21A2 Point Mutations in the Republic of Macedonia

“…Finally, two mild mutations, V281L and P30L, were found on 2.1% of alleles in one compound heterozygote each ( Table 2). The distribution of the detected mutations in our study was slightly different from those previously reported from large populations [16][17][18][19][20] . No 8 base-pair deletion, I172N, E6 cluster and F306+t were detected in the analysed subjects.…”

Mutation distributions among patients with congenital adrenal hyperplasia from five regions of Brazil: a systematic review

“…Interestingly, a significant proportion of novel mutations were identified in our Brazilian populations that were not derived from pseudogene conversion events. Novel mutations notable in the North, Center-West, and Southeast regions (24,27,(29)(30)(31)(32). These findings also reflect the presence of a founder effect gene.…”

“…The PRISMA flow diagram (Figure 1) summarizes the literature search. Numbers of articles found per region were one from the North region (24), two from the Northeast (25,26), one from the Central West (27), one from the South (28), and four from the Southeast (29)(30)(31)(32). Notably, only neonatal screening studies were available from the South region.…”

“…A lower prevalence of LGR was seen, except in the Center-West and South regions, where it was considerably higher. LGR was not screened in studies performed in the North and Northeast regions, which provides a partial explanation for these differences (24)(25)(26). CYP21A2 deletions were associated with classical CAH, and the lower prevalence observed in some regions might suggest that SW neonates were not properly diagnosed in the absence of neonatal screening.…”

“…The Brazilian population displayed some differences in comparison to Caucasian populations. For instance, a higher prevalence of the p.Q318X mutation was reported in the North, Northeast, and Center-West patients (24)(25)(26)(27). IVS2-13A/C>G is the most prevalent mutation in various ethnic populations, and is the most frequent pathogenic variant in Brazilian regions, especially among SW patients.…”