title: Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.
abstract: Bartter's syndrome is a heterogeneous disorder characterised by deficient renal reabsorption of sodium and chloride, and hypokalaemic metabolic alkalosis with hyper-reninaemia and hyperaldosteronaemia. Mutations in several ion transporters and channels have been associated with the pathogenesis of Bartter's syndrome. We describe two hypocalcaemic patients with deficient parathyroid hormone secretion who also showed characteristics of Bartter's syndrome. We found activating mutations of the gene for the calcium-sensing receptor (CASR) in both patients. Activation of this calcium-sensing receptor inhibits the activity of a renal outer-medullary potassium channel that is mutated in type 2 Bartter's syndrome. We therefore suggest that some activating mutations of CASR could provide new mechanisms for the development of Bartter's syndrome.
authors.affiliation: Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Watanabe
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukumoto
authors.forename: Hangil
authors.initials: H
authors.lastname: Chang
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Okazaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Chikatsu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000328:Adult; D001477:Bartter Syndrome / Q000097:blood / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000150:complications; D007011:Hypoparathyroidism / Q000150:complications; D008297:Male; D009154:Mutation; D010281:Parathyroid Hormone / Q000172:deficiency; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface