Primary aldosteronism associated with a germline variant in CACNA1H. Issue 5 (23rd May 2019)

• Record Type: Journal Article
• Authors: Wulczyn, Kendra; Perez-Reyes, Edward; Nussbaum, Robert L; Park, Meyeon
• Is Part Of: BMJ case reports. Volume 12:Issue 5(2019)
• Publication Date: 2019-05-23
• Subjects: fluid electrolyte and acid–base disturbances -- genetics -- adrenal disorders; Medicine -- Case studies -- Periodicals; 610.5
• DOI: 10.1136/bcr-2018-229031
• Languages: English
• ISSNs: 1757-790X

Abstract

Abstract : The CACNA1H gene encodes the pore-forming α1 subunit of the T-type voltage-dependent calcium channel CaV 3.2, expressed abundantly in the adrenal cortex. Mutations in CACNA1H are associated with various forms of primary aldosteronism (PA), including familial hyperaldosteronism type 4 (FH4). We describe a patient with refractory hypokalaemia and elevated aldosterone secretion independent of renin activity. Despite the absence of overt hypertension in this patient, the laboratory evaluation was consistent with a diagnosis of PA. Whole-exome sequencing revealed a de novo missense variant, R890H, in the voltage sensing domain of CACNA1H . Expression of the variant channel in cells resulted in decreased whole-cell current, consistent with a loss-of-function. We hypothesise this variant is the genetic cause of pathological aldosterone secretion in this patient, and thereby expand the current understanding of the genetic basis of FH4.