{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:33Z","timestamp":1791923913296,"version":"4.3.4"},"reference-count":133,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>\n                    Primary aldosteronism (PA), the most common form of secondary hypertension, is caused in the majority of cases by unilateral aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia. Over the past few years, somatic mutations in\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    ,\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    ,\n                    <jats:italic>ATP1A1<\/jats:italic>\n                    and\n                    <jats:italic>ATP2B3<\/jats:italic>\n                    have been proven to be associated with APA development, representing more than 50% of sporadic APA. The identification of these mutations has allowed the development of a model for APA involving modification on the intracellular ionic equilibrium and regulation of cell membrane potential, leading to autonomous aldosterone overproduction. Furthermore, somatic\n                    <jats:italic>CTNNB1<\/jats:italic>\n                    mutations have also been identified in APA, but the link between these mutations and APA development remains unknown. The sequence of events responsible for APA formation is not completely understood, in particular, whether a single hit or a double hit is responsible for both aldosterone overproduction and cell proliferation. Germline mutations identified in patients with early-onset PA have expanded the classification of familial forms (FH) of PA. The description of germline\n                    <jats:italic>KCNJ5<\/jats:italic>\n                    and\n                    <jats:italic>CACNA1H<\/jats:italic>\n                    mutations has identified FH-III and FH-IV based on genetic findings; germline\n                    <jats:italic>CACNA1D<\/jats:italic>\n                    mutations have been identified in patients with very early-onset PA and severe neurological abnormalities. This review summarizes current knowledge on the genetic basis of PA, the association of driver gene mutations and clinical findings and in the contribution to patient care, plus the current understanding on the mechanisms of APA development.\n                  <\/jats:p>","DOI":"10.1530\/jme-17-0035","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T20:10:33Z","timestamp":1491941433000},"page":"R47-R63","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":50,"title":["Somatic and inherited mutations in primary aldosteronism"],"prefix":"10.1530","volume":"59","author":[{"given":"Fabio Luiz","family":"Fernandes-Rosa","sequence":"first","affiliation":[{"name":"1INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France"},{"name":"2University Paris DescartesSorbonne Paris Cit\u00e9, Paris, France"},{"name":"3Assistance Publique-H\u00f4pitaux de ParisH\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheerazed","family":"Boulkroun","sequence":"additional","affiliation":[{"name":"1INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France"},{"name":"2University Paris DescartesSorbonne Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Christina","family":"Zennaro","sequence":"additional","affiliation":[{"name":"1INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France"},{"name":"2University Paris DescartesSorbonne Paris Cit\u00e9, Paris, France"},{"name":"3Assistance Publique-H\u00f4pitaux de ParisH\u00f4pital Europ\u00e9en Georges Pompidou, Service de G\u00e9n\u00e9tique, Paris, 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