Association between activating mutations of calcium-sensing receptor and Bartter's syndrome.
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.
Watanabe
Sumiyo
S
Department of Internal Medicine, University of Tokyo School of Medicine, Tokyo, Japan.
Fukumoto
Seiji
S
Chang
Hangil
H
Takeuchi
Yasuhiro
Y
Hasegawa
Yukihiro
Y
Okazaki
Ryo
R
Chikatsu
Noriko
N
Fujita
Toshiro
T
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*
D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D011956:Receptors, Cell Surface