Classic Steroid 11β-Hydroxylase Deficiency Caused by a C→G Transversion in Exon 7 of CYP11B1

Steroid 11β-hydroxylase deficiency (11βOHD) is derived from mutations in the P450_11β gene (CYP11B1) and inherited in an autosomal recessive manner. In the present study, we have performed a molecular genetic analysis of CYP11B1 in a Japanese patient clinically diagnosed as classic 11βOHD. Nucleotide sequencing of the PCR-amplified exons from the patient′s genomic DNA reveals a unique C→G transversion that converts codon 384 CGA (arginine) to GGA (glycine) in exon 7. Restriction fragment length polymorphism (RFLP) data demonstrate that the patient is homozygous for this mutation. When the full-length cDNA corresponding to CYP11B1 of the patient is transfected into COS-7 cells, no steroid 11 beta-hydroxylase activity is detectable in mitochondria of the cells. These results indicate that this point mutation completely abolishes P450_11β activity and causes the classic 11βOHD.