title: Inactivating mutations of the mineralocorticoid receptor in Type I pseudohypoaldosteronism.
abstract: Type I pseudohypoaldosteronism (PHA1) is a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive. Typical biochemical features include high levels of plasma aldosterone and renin, hyponatremia and hyperkalemia. Different mutations of the human mineralocorticoid receptor (hMR) gene have been identified in subjects affected by the autosomal dominant or sporadic form of the disease. Our laboratory has investigated a large number of subjects with familial and sporadic PHA1. Several different mutations have been detected, which are localized in different coding exons of the hMR gene. These mutations either create truncated proteins, either affect specific amino acids involved in receptor function. In this paper, we review hMR mutations described to date in PHA1 and their functional characterization. We discuss the absence of mutations in some kindreds and the role of precise phenotypic and biological examination of patients to allow for identification of other genes potentially involved in the disease.
authors.affiliation: INSERM U 478, Faculté de Médecine Xavier Bichat, B.P. 416, 16 rue Henri HUCHARD, 75870 Paris Cedex 18, France.
authors.forename: P
authors.initials: P
authors.lastname: Sartorato
authors.forename: Y
authors.initials: Y
authors.lastname: Khaldi
authors.forename: A-L
authors.initials: AL
authors.lastname: Lapeyraque
authors.forename: D
authors.initials: D
authors.lastname: Armanini
authors.forename: U
authors.initials: U
authors.lastname: Kuhnle
authors.forename: R
authors.initials: R
authors.lastname: Salomon
authors.forename: M
authors.initials: M
authors.lastname: Caprio
authors.forename: S
authors.initials: S
authors.lastname: Viengchareun
authors.forename: M
authors.initials: M
authors.lastname: Lombès
authors.forename: M-C
authors.initials: MC
authors.lastname: Zennaro
mesh_terms: D000450:Aldosterone / Q000097:blood; D005091:Exons / Q000235:genetics*; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D007008:Hypokalemia / Q000235:genetics / Q000503:physiopathology; D007010:Hyponatremia / Q000235:genetics / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008901:Mineralocorticoids / Q000378:metabolism; D009154:Mutation; D010375:Pedigree; D011237:Predictive Value of Tests; D011546:Pseudohypoaldosteronism / Q000097:blood / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology; D018161:Receptors, Mineralocorticoid / Q000235:genetics* / Q000378:metabolism; D012083:Renin / Q000097:blood; D012492:Salts / Q000378:metabolism
chemical_list: D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D012492:Salts; D000450:Aldosterone; D012083:Renin