The molecular biology of congenital adrenal hyperplasia in the Mediterranean area

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is one of the most common autosomal recessive metabolic disease and occurs worldwide. Ethnic-specific differences in the distribution of CYP21A2 gene mutations have been described so far. In this report we focused our attention to the Mediterranean area and compared the types and the relative frequencies of molecular defects in 233 unrelated patients of Italian origin (as defined by review of pedigrees extending to two or three generations) with the reported frequencies in other “Mediterranean” Countries. In particular, the distribution of mutations were available for samples of Croatian, French, Hellenic, Lebanese, Slovenian, Spanish, Tunisian, and Turkish populations. The predominance of the prevalent allelic mutations and genotypes in some of these populations was significant and it appeared that ethnic- or even intra-ethnic specific mutations were present. A large deletion is prevalent in the Slovenjans; a Q318X mutation is prevalent in the Tunisians; a R356W is prevalent in the Croatians; the D8bp mutation was rather frequent in the Lebanese population and exclusively in the Christian Maronite group. Intra-National differences were also found when the comparison was extended to groups coming from different areas of the same Nation such as North-West vs. Central Spain or North-Central vs. South Italy. The more frequent genotype/phenotype discrepancies will be discussed.