A chimeric CYP11B1/CPY11B2 gene in glucocorticoid-insuppressible familial hyperaldosteronism

Although a chimeric gene combining the 11β-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2) explains the pathophysiology of familial hyperaldosteronism (FH) type I, the contribution of this abnormality to FH type II has not been tested. We screened genomic DNA from a Japanese family with FH type II for the CYP11B1/CYP11B2 gene. The index patient was a 27-year-old woman with hypertension. Hypokalaemia, elevated plasma aldosterone and suppressed plasma renin activity suggested primary aldosteronism. Though computed tomography failed to reveal an adrenal tumour, left adrenalectomy was indicated due to a high aldosterone concentration in left adrenal venous blood. The resected adrenal gland contained an adenoma. As her mother had also been diagnosed with primary aldosteronism due to an adenoma, we administered oral dexamethasone to our patient before the operation and observed the response of the blood pressure and plasma aldosterone concentration for 2 weeks. Both parameters remained elevated during the treatment period, confirming the diagnosis of FH type II. Total DNA was isolated from blood cells of the index patient, her mother, and an unaffected brother. Samples were amplified by polymerase chain reaction using specific primers from CYP11B1 and CYP11B2. Unique DNA fragments of 1.4 kb were obtained from the index patient and her mother, but not from the healthy subject. The CYP11B1/CYP11B2 chimeric gene was found in a Japanese family with FH type II.