Genetic Analyses of the Chimeric CYP11B1 / CYP11B2 Gene in a Korean Family with Glucocorticoid-Remediable Aldosteronism

• Published in: Journal of Korean medical science Vol. 25; no. 9; pp. 1379 - 1383
• Main Authors: Lee, Ihn Suk, Kim, Seul Young, Jang, Hye Won, Kim, Min Kyeong, Lee, Ju Hee, Lee, Yun Hyeong, Jo, Young Suk
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Medical Sciences 01.09.2010; 대한의학회
• Subjects: Adolescent; Aldosterone - blood; Asian Continental Ancestry Group - genetics; Case Report; Cytochrome P-450 CYP11B2 - genetics; Dexamethasone - therapeutic use; Family; Female; Glucocorticoids - therapeutic use; Humans; Hyperaldosteronism - diagnosis; Hyperaldosteronism - drug therapy; Hyperaldosteronism - genetics; Hypertension - etiology; Magnetic Resonance Angiography; Male; Middle Aged; Renin - blood; Renin - metabolism; Republic of Korea; Sequence Analysis, DNA; Steroid 11-beta-Hydroxylase - genetics; Young Adult; 의학일반; Republic of Korea; Hyperaldosteronism; Aldosterone Synthase; Steroid 11-beta-Hydroxylase
• ISSN: 1011-8934; 1598-6357; 1598-6357
• DOI: 10.3346/jkms.2010.25.9.1379

Glucocorticoid-remediable aldosteronism (GRA) is an autosomal-dominant inheritable form of hyperaldosteronism with early onset hypertension. GRA is caused by unequal crossing-over of the steroid 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. As a result of chimeric gene duplication, aldosterone is ectopically synthesized in the adrenal zona fasciculata under the control of adrenocorticotropin. Here, we describe three cases of GRA in a Korean family. The proband-a 21-yr-old female-was incidentally found to have high blood pressure (170/108 mmHg). Her 46-yr-old father had been treated twice for cerebral hemorrhage at the ages of 29 and 39 yr. Her 15-yr-old brother had a 2-yr history of hypertension; however, he was never treated. Their laboratory test results showed normokalemia, hyporeninemia, hyperaldosteronism, and a high plasma aldosterone concentration-to-plasma renin activity ratio. Normal saline loading failed to suppress aldosterone secretion. However, dexamethasone administration effectively suppressed their plasma aldosterone concentrations. Following genetic analyses with PCR and direct sequencing to document the chimeric gene and crossover site, respectively, we identified CYP11B1/CYP11B2 and determined the breakpoint of unequal crossover to be located between intron 2 of CYP11B1 and exon 3 of CYP11B2.