title: 30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor mutations.
abstract: Aldosterone and the mineralocorticoid receptor (MR) are key elements for maintaining fluid and electrolyte homeostasis as well as regulation of blood pressure. Loss-of-function mutations of the MR are responsible for renal pseudohypoaldosteronism type 1 (PHA1), a rare disease of mineralocorticoid resistance presenting in the newborn with weight loss, failure to thrive, vomiting and dehydration, associated with hyperkalemia and metabolic acidosis, despite extremely elevated levels of plasma renin and aldosterone. In contrast, a MR gain-of-function mutation has been associated with a familial form of inherited mineralocorticoid hypertension exacerbated by pregnancy. In addition to rare variants, frequent functional single nucleotide polymorphisms of the MR are associated with salt sensitivity, blood pressure, stress response and depression in the general population. This review will summarize our knowledge on MR mutations in PHA1, reporting our experience on the genetic diagnosis in a large number of patients performed in the last 10 years at a national reference center for the disease. We will also discuss the influence of rare MR variants on blood pressure and salt sensitivity as well as on stress and cognitive functions in the general population.
authors.affiliation: INSERMParis Cardiovascular Research Center, Paris, France maria-christina.zennaro@inserm.fr.|Université 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
authors.affiliation: INSERMParis Cardiovascular Research Center, Paris, France.|Université Paris DescartesSorbonne Paris Cité, Paris, France.|Assistance Publique-Hôpitaux de ParisHôpital Européen Georges Pompidou, Service de Génétique, Paris, France.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fernandes-Rosa
mesh_terms: D000450:Aldosterone / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D011546:Pseudohypoaldosteronism / Q000235:genetics* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D018161:Receptors, Mineralocorticoid; D000450:Aldosterone
keywords: aldosterone; hormone receptors; mineralocorticoid receptor; nuclear receptor; pseudohypoaldosteronism type 1- PHA1