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Mulatero, P.* ; Tauber, P.* ; Zennaro, M.C.* ; Monticone, S.* ; Lang, K.* ; Beuschlein, F.* ; Fischer, E.* ; Tizzani, D.* ; Pallauf, A.* ; Viola, A.* ; Amar, L.* ; Williams, T.A.* ; Strom, T.M. ; Graf, E. ; Bandulik, S.* ; Penton, D.* ; Plouin, P.F.* ; Warth, R.* ; Allolio, B.* ; Jeunemaitre, X.* ; Veglio, F.* ; Reincke, M.*

KCNJ5 mutations in European families with nonglucocorticoid remediable familial hyperaldosteronism.

Hypertension 59, 235-240 (2012)
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Primary aldosteronism is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in 2 primary aldosteronism-affected subjects from an Italian family and 3 somatic mutations in aldosterone-producing adenomas, T158A described previously as a germline mutation associated with FH-III, and G151R and L168R both described as somatic mutations in aldosterone-producing adenoma. The phenotype of the family with the G151E mutation was remarkably milder compared with the previously described American family, in terms of both clinical and biochemical parameters. Furthermore, patients with somatic KCNJ5 mutations displayed a phenotype indistinguishable from that of sporadic primary aldosteronism. The functional characterization of the effects of the G151E mutation in vitro showed a profound alteration of the channel function, with loss of K(+) selectivity, Na(+) influx, and membrane depolarization. These alterations have been postulated to be responsible for voltage gate Ca(2+) channel activation, increase in cytosolic calcium, and stimulation of aldosterone production and adrenal cell proliferation. In conclusion, we describe herein a new mutation in the KCNJ5 potassium channel associated with FH-III, responsible for marked alterations of channel function but associated with a mild clinical and hormonal phenotype.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter familial hyperaldosteronism; endocrine hypertension; primary aldosteronism; aldosterone; KCNJ5
Sprache englisch
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0194-911x
e-ISSN 1524-4563
Zeitschrift Hypertension
Quellenangaben Band: 59, Heft: 2, Seiten: 235-240 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
PubMed ID 22203740
DOI 10.1161/HYPERTENSIONAHA.111.183996
WOS ID WOS:000299315800026
Scopus ID 84856300896
Erfassungsdatum 2012-04-11
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