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Steroid 110-hydroxylase (P-450118) is a mitochondrial cytochrome P-450 enzyme necessary for cortisol biosynthesis.Deficiency of 1 10-hydroxylase causes a hypertensive form of congenital adrenal hyperplasia.A partial cDNA clone encoding this enzyme has been previously isolated and the corresponding gene, CYP11B1, mapped to human chromosome 8q.This gene has now been isolated along with a second linked homologous gene, CYPllB2.Each gene contains nine exons.The eight introns are identical in location to the introns of the CYPllA gene encoding another mitochondrial P-450 enzyme, cholesterol desmolase, confirming that 1 10-hydroxylase and cholesterol desmolase are in the same gene family within the P-450 superfamily.The nucleotide sequences of CYPllBl and B2 are 95% identical in coding regions and about 90% identical in introns.The putative proteins encoded by CYPllBl and B2 each contain 503 amino acids including a 24-residue signal peptide and have sequences that are 93% identical to each other and 75% identical to the predicted sequence of bovine P-45Oll8.There are no obviously deleterious mutations in coding sequences of CYPllB2.However, the 5"flanking regions of CYPllBl and B2 have diverged considerably, and B2 transcripts were not detected in human adrenal mRNA or among cDNA clones.Congenital adrenal hyperplasia is a disease caused by an inherited defect in cortisol biosynthesis (1).Cortisol is normally synthesized from cholesterol in the zona fasciculata of the adrenal cortex in five enzymatic steps: the cholesterol side chain is cleaved by cholesterol desmolase to form pregnenolone, which is dehydrogenated at the 30 position to yield progesterone; three successive hydroxylations at the 17~1, 21, and l l p positions yield cortisol.More than 90% of cases of congenital adrenal hyperplasia are caused by impaired 21- hydroxylation.The molecular genetic basis of 21-hydroxylase deficiency has been extensively studied (1, 2).In 5-8% of reported cases of congenital adrenal hyperplasia, llp-hydroxylation is defective, so that 11-deoxycortisol can-
Mornet et al. (Fri,) studied this question.