title: Somatic and inherited mutations in primary aldosteronism.
abstract: 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 inKCNJ5,CACNA1D,ATP1A1andATP2B3have 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, somaticCTNNB1mutations 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 germlineKCNJ5andCACNA1Hmutations has identified FH-III and FH-IV based on genetic findings; germlineCACNA1Dmutations 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.
authors.affiliation: INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France.|University Paris DescartesSorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de ParisHôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Fabio Luiz
authors.initials: FL
authors.lastname: Fernandes-Rosa
authors.affiliation: INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France.|University Paris DescartesSorbonne Paris Cité, Paris, France.
authors.forename: Sheerazed
authors.initials: S
authors.lastname: Boulkroun
authors.affiliation: INSERMUMRS_970, Paris Cardiovascular Research Center, Paris, France.|University Paris DescartesSorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de ParisHôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Zennaro
mesh_terms: D000236:Adenoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D000312:Adrenal Hyperplasia, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D006929:Hyperaldosteronism / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007008:Hypokalemia / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C472073:CACNA1D protein, human; C495270:CTNNB1 protein, human; D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D051176:beta Catenin; C499076:ATP1A1 protein, human; D053499:Plasma Membrane Calcium-Transporting ATPases; C506962:ATP2B3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
keywords: ATPase; Wnt/β-catenin pathway; aldosterone-producing adenoma; calcium channels; familial hyperaldosteronism; germline mutations; potassium channels; primary aldosteronism; somatic mutations