Mutations in CYP11B1 and congenital adrenal hyperplasia in Moroccan Jews

Context: In Jews of Moroccan descent (MJ), the prevalence of steroid 11 beta-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 11 beta-hydroxylase), R448H, was suggested to account for the disease alleles in this population. Study Subjects: We screened 236 healthy MJ for R448H. Results: 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. Conclusion: The high incidence of 11-OHD in MJ, therefore, is only partially explained by the presence of R448H as a founder mutation.