Dokumentenart: | Artikel | ||||
---|---|---|---|---|---|
Titel eines Journals oder einer Zeitschrift: | Hypertension | ||||
Verlag: | LIPPINCOTT WILLIAMS & WILKINS | ||||
Ort der Veröffentlichung: | PHILADELPHIA | ||||
Band: | 59 | ||||
Nummer des Zeitschriftenheftes oder des Kapitels: | 2 | ||||
Seitenbereich: | S. 235-240 | ||||
Datum: | 2012 | ||||
Institutionen: | Biologie und Vorklinische Medizin > Institut für Physiologie Biologie und Vorklinische Medizin > Institut für Physiologie > Prof. Dr. Richard Warth | ||||
Identifikationsnummer: |
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Stichwörter / Keywords: | PRIMARY ALDOSTERONISM; DIFFERENTIAL-DIAGNOSIS; CHROMOSOME 7P22; CORTISOL; CRITERIA; FORM; familial hyperaldosteronism; endocrine hypertension; primary aldosteronism; aldosterone; KCNJ5 | ||||
Dewey-Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie | ||||
Status: | Veröffentlicht | ||||
Begutachtet: | Ja, diese Version wurde begutachtet | ||||
An der Universität Regensburg entstanden: | Ja | ||||
Dokumenten-ID: | 64078 |
Zusammenfassung
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 ...
Zusammenfassung
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 Ca2(+) 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. (Hypertension. 2012; 59: 235-240.). Online Data Supplement
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