A large view of CYP21 locus among Sicilians and other Populations: identification of a novel CYP21A2 variant in Sicily

Background. Several mutations in CYP21 locus cause 21-Hydroxylase Deficiency (21-OHD). The most common mutations are widespread among the different geographic areas and their frequencies have been also reported to differ among certain populations. Aim. To obtain a large view on the frequencies of the most common mutations in the CYP21 locus, in Sicily, in Mediterranean and in other major geographic areas in the worldwide. Subjects and Methods. 308 unrelated CYP21A2 alleles leading 21-OHD in Sicily were genetically typed and compared with other series previously reported in Sicily and in surrounding regions. An analysis of the frequencies of the different geographic areas was also carried out. CYP21A2 typing was carried out using PCR-RFLP, for the detection of the CYP21A2 deletion, while sequencing analysis was performed to evaluate all the missense/non-sense mutations. Results: our study revealed that p.V281L (44.4%), I2splice (21.6%) and p.P30L (11.2%) were very frequent alleles, del8bp (0.4%) was found very rarely in Sicily and a novel mutation leading to nonclassical phenotype, p.L198F, was also discovered in this population. Allele frequencies were found to be significantly different from previously observed frequencies in Sicily. In addition, here we present the most significant frequency modifications among different geographic areas in the worldwide. Conclusions: as the distribution of the disease CYP21A2 alleles is heterogeneous around the world, the knowledge of the relative distributions allows a better management of 21-OHD for foetuses and newborns in different geographic areas.