CYP11B1, CYP11B1/CYP11B2 CHIMERA AND Deficiency of steroid 11-beta-monooxygenase

Significance: Pathogenic
ClinVar: RCV000001241

Variant: CYP11B1, CYP11B1/CYP11B2 CHIMERA

Type: Variant
Allele: CYP11B1, CYP11B1/CYP11B2 CHIMERA 16221
Type: Deletion
References: OMIM: 610613.0012


Disease: Deficiency of steroid 11-beta-monooxygenase


    Hampf et al. (2001) reported a case of steroid 11-beta-hydroxylase deficiency (202010) caused by an unequal crossover of the genes encoding aldosterone synthase (CYP11B2; 124080) and 11-beta-hydroxylase (CYP11B1). CYP11B1 and CYP11B2 are located on chromosome 8q24 approximately 45 kb apart from each other. The investigated genetic recombination deleted the normal alleles of the 2 genes and created a chimeric fusion gene, which consists of the promoter and exons 1 through 4 of the CYP11B2 gene plus intron 4 through exon 9 of the CYP11B1 gene. This recombination event subordinated any remaining CYP11B1 activity of the chimeric enzyme to the control mechanisms of CYP11B2, the expression of which is mainly regulated by angiotensin II (see 106150) and potassium. Normally the CYP11B1 activity is controlled by ACTH. Furthermore, by applying a minigene expression method, Hampf et al. (2001) demonstrated a point mutation in intron 3 (IVS3+16G-T; 610613.0013) of the patient's second CYP11B1 allele that radically diminished proper splicing of the pre-mRNA by giving rise to a new, highly preferred donor splice site.