Mutations in CYP11B1 and congenital adrenal hyperplasia in Moroccan Jews.

Abstract

In Jews of Moroccan descent (MJ), the prevalence of steroid 11beta-hydroxylase deficiency (11-OHD) is relatively high, with a carrier rate estimated as approximately one in 40. A single mutation in the CYP11B1 gene (encoding 11beta-hydroxylase), R448H, was suggested to account for the disease alleles in this population. We screened 236 healthy MJ for R448H. Only two of the subjects screened were found to be carriers, suggesting that the R448H allele frequency is lower than was assumed previously. An R448H/R448C compound heterozygote patient, diagnosed with 11-OHD, was identified. However, a subsequent screen of MJ subjects for R448C failed to detect any carriers, suggesting that this was a private mutation of this family. The high incidence of 11-OHD in MJ, therefore, is only partially explained by the presence of R448H as a founder mutation.