ICEECE2012 Poster Presentations Adrenal cortex (113 abstracts)
KCNJ5 Mutations in European Families with Non-Glucocorticoid Remediable Familial Hyperaldosteronism
P. Mulatero 1 , P. Tauber 2 , M. Zennaro 3 , S. Monticone 1 , K. Lang 4 , F. Beuschlein 5 , E. Fischer 5 , J. Burrello 1 , A. Pallauf 5 , M. Galmozzi 1 , L. Amar 3 , T. Williams 1 , T. Strom 6 , E. Graf 6 , S. Bandulik 2 , D. Penton 2 , P. Plouin 3 , R. Warth 2 , B. Allolio 4 , X. Jeunemaitre 3 , F. Veglio 1 & M. Reincke 5
1University of Torino, Torino, Italy; 2University of Regensburg, Regensburg, Germany; 3Paris Cardiovascular Research Center, Paris, France; 4University Hospital Würzburg, Würzburg, Germany; 5Klinikum der LMU, Munich, Germany; 6Helmholtz Zentrum München, Munich, Germany.
Primary Aldosteronism (PA) 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 two PA affected subjects from an Italian family and three somatic mutations in aldosterone-producing adenomas (APA), T158A previously described as a germline mutation associated with FH-III, and G151R and L168R both described as somatic mutations in APA. The phenotype of the family with the G151E mutation was remarkably milder compared to 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 PA. 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 Ca2+ channel activation, increase in cytosolic calcium and stimulation of aldosterone production and adrenal cells 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.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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