title: New genetic insights in familial hyperaldosteronism.
abstract: Aldosterone, the major circulating mineralocorticoid, particiates in blood volume and serum potassium homeostasis. Primary aldosteronism is a disorder characterized by hypertension and, in more severe form, hypokalemia, due to autonomous aldosterone secretion from the adrenocortical zona glomerulosa. Improved screening techniques, particularly application of the plasma aldosterone: plasma renin activity ratio, has led to renewed interest in Conn's original proposal that primary aldosteronism may be the cause of increased blood pressure in about 10% of adults with hypertension. Glucocorticoid-remediable aldosteronism (GRA) was the first described familial form of hyperaldosteronism. The disorder is characterized by aldosterone secretory function regulated chronically by ACTH. Hence, aldosterone hypersecretion can be chronically suppressed by exogenous glucocorticoids such as dexamethasone in physiologic-range doses. This autosomal dominant disorder has been shown to be caused by a hybrid gene mutation formed by a cross-over of genetic material between the ACTH-responsive regulatory portion of the 11b-hydroxylase (CYP11B1) gene and the coding region of the aldosterone synthase (CYP11B2) gene. Familial hyperaldosteronism type II (FH-II), so named to distinguish the disorder from GRA or familial hyperaldosteronism type I (FH-I), is characterized by inheritance consistent with an autosomal dominant pattern of autonomous aldosterone hypersecretion which is not suppressible by dexamethasone. Linkage analysis in a single large kindred, and direct mutation screening, has shown that this disorder is unrelated to mutations in the genes for aldosterone synthase or the angiotensin II receptor. A recent genome-wide search has identified a genetic linkage between FH-II in this single large kindred and polymorphic gene markers on chromosome 7 in a region that corresponds to cytogenetic band 7p22. This is the first identified locus for FH-II. Several possible candidate genes have been localized to the 7p22 region. The precise genetic cause of FH-II remains to be elucidated.
authors.affiliation: Department of Medicine, University of Queensland, Greenslopes Private Hospital, Newdegate Street, Brisbane, Queensland 4120, Australia. r.jackson@mailbox.uq.edu.au
authors.forename: Richard V
authors.initials: RV
authors.lastname: Jackson
authors.forename: Anthony
authors.initials: A
authors.lastname: Lafferty
authors.forename: David J
authors.initials: DJ
authors.lastname: Torpy
authors.forename: Constantine
authors.initials: C
authors.lastname: Stratakis
mesh_terms: D000303:Adrenal Cortex Diseases / Q000235:genetics* / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D002897:Chromosomes, Human, Pair 7; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D006801:Humans; D006929:Hyperaldosteronism / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D006973:Hypertension / Q000209:etiology; D007008:Hypokalemia / Q000209:etiology; D012083:Renin / Q000097:blood
chemical_list: D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D012083:Renin