Missense mutation in CYP11B1 (CGA[Arg-384]-->GGA[Gly]) causes steroid 11 beta-hydroxylase deficiency.

Steroid 11 beta-hydroxylase deficiency (11 beta-OHD) is an autosomal recessive hereditary defect and one of the causes of congenital adrenal hyperplasia. The 11 beta-hydroxylase enzyme is encoded by the CYP11B1 gene on chromosome 8q22. Twelve types of mutations of this gene have been reported previously in patients with 11 beta-OHD, including one Japanese patient. We detected an additional previously uncharacterized mutation: R384G mutation, a single C-->G base substitution in the codon 384 of the exon 7 changing an arginine (CGA) to a glycine (GGA) by sequencing the CYP11B1 gene of Japanese siblings with 11 beta-OHD. We analyzed also the CYP11B1 gene of their unaffected family members. Their grandfather was homozygous for the normal gene, whereas their grandmother, parents and younger brother were heterozygous for the mutation. These results indicate that the cause of 11 beta-OHD is heterogeneous even in the Japanese population, which is ethnically homogeneous.