期刊
JOURNAL OF MOLECULAR ENDOCRINOLOGY
卷 59, 期 1, 页码 R47-R63出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-17-0035
关键词
primary aldosteronism; aldosterone-producing adenoma; familial hyperaldosteronism; somatic mutations; germline mutations; potassium channels; calcium channels; ATPase; Wnt/beta-catenin pathway
资金
- INSERM
- Agence Nationale pour la Recherche [11-BSV1 005 03, ANR-13-ISV1-0006-01]
- Fondation pour la Recherche Medicale [DEQ20140329556]
- Programme Hospitalier de Recherche Clinique (PHRC) [AOM 06179]
- INSERM and Ministere Delegue a la Recherche et des Nouvelles Technologies
- ENSAT-HT [633983]
- Agence Nationale de la Recherche (ANR) [ANR-13-ISV1-0006] Funding Source: Agence Nationale de la Recherche (ANR)
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 KCNJ5, CACNA1D, ATP1A1 and ATP2B3 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 CTNNB1 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 KCNJ5 and CACNA1H mutations has identified FH-III and FH-IV based on genetic findings; germline CACNA1D 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.
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