title: Genetics of primary aldosteronism.
abstract: Primary aldosteronism (PA) accounts for ∼10% of hypertension, which is commonly caused by an aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Germline mutations producing PA are considered rare and termed familial hyperaldosteronism (FH) [1, 2, 3]. Since early 2011, a series of somatic mutations confined to the adrenal cortex has been reported, accounting for about half of APA. These mutations are in genes encoding components of the Kir 3.4 (GIRK4) potassium channel (KCNJ5), sodium/potassium and calcium ATPases (ATP1A1 and ATP2B3) and a voltage-dependent C-type calcium channel (CACNA1D). FH-1 (glucocorticoid-remediable hyperaldosteronism) results from a chimeric gene (5'-end of CYP11B1 fused to 3'-end of CYP11B2) and accounts for ∼1% of PA. FH-3 is very rare, is caused by bilateral expression of mutant KCNJ5 and usually results in florid hyperaldosteronism requiring early bilateral adrenalectomy. FH-2 is the most common form of hereditary PA (2 first-degree relatives with either an APA or bilateral adrenal hyperplasia) and currently thought to represent ∼6% of PA; the true prevalence may be considerably higher. The mutation(s) causing FH-2 are unknown but appear dominant, as is the case for FH-1 and FH-3. No studies have been done on possible recessive forms of PA.
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Vic., Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Funder
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000235:genetics*; D019943:Amino Acid Substitution; D020746:Calcium Channels, L-Type / Q000235:genetics; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D006801:Humans; D006929:Hyperaldosteronism / Q000235:genetics*; D008297:Male; D053499:Plasma Membrane Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics
chemical_list: C472073:CACNA1D protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase