CLASSIC STEROID 11-BETA-HYDROXYLASE DEFICIENCY CAUSED BY A C-]G TRANSVERSION IN EXON-7 OF CYP11B1

Steroid 11 beta-hydroxylase deficiency (11 beta OHD) is derived from m utations in the P450(11 beta) gene (CYP11B1) and inherited in an autos omal recessive manner. In the present study, we have performed a molec ular genetic analysis of CYP11B1 in a Japanese patient clinically diag nosed as classic 11 beta OHD. Nucleotide sequencing of the PCR-amplifi ed exons from the patient's genomic DNA reveals a unique C-->G transve rsion that converts codon 384 (C) under bar GA (arginine) to (G) under bar GA (glycine) in exon 7. Restriction fragment length polymorphism (RFLP) data demonstrate that the patient is homozygous for this mutati on. When the full-length cDNA corresponding to CYP11B1 of the patient is transfected into COS-7 cells, no steroid 11 beta-hydroxylase activi ty is detectable in mitochondria of the cells. These results indicate that this point mutation completely abolishes P450(11 beta) activity a nd causes the classic 11 beta OHD. (C) 1995 Academic Press, Inc.