GENETIC-HETEROGENEITY OF BARTTERS-SYNDROME REVEALED BY MUTATIONS IN THE K+ CHANNEL, ROMK

Mutations in the Na-K-2Cl cotransporter (NKCC2), a mediator of renal s alt reabsorption, cause Bartter's syndrome, featuring salt wasting, hy pokalaemic alkalosis, hypercalciuria and low blood pressure. NKCC2 mut ations can be excluded in some Bartter's kindreds, prompting examinati on of regulators of cotransporter activity. One regulator is believed to be ROMK, an ATP-sensitive K+ channel that 'recycles' reabsorbed Kback to the tubule lumen, Examination of the ROMK gene reveals mutatio ns that co-segregate with the disease and disrupt ROMK function in fou r Bartter's kindreds. Our findings establish the genetic heterogeneity of Bartter's syndrome, and demonstrate the physiologic role of ROMK i n vivo.