Genetic heterogeneity of Bartter's syndrome revealed by mutations in the K+ channel, ROMK

• Published in: Nature genetics Vol. 14; no. 2; pp. 152 - 156
• Main Authors: SIMON, D. B, KARET, F. E, RODRIGUEZ-SORIANO, J, HAMDAN, J. H, DIPIETRO, A, TRACHTMAN, H, SANJAD, S. A, LIFTON, R. P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-10-1996
• Subjects: Amino Acid Sequence; Bartter Syndrome - genetics; Biological and medical sciences; Carrier Proteins - genetics; Cell Membrane - chemistry; Consanguinity; Conserved Sequence; DNA Mutational Analysis; Female; Genetic Heterogeneity; Genotype; Glomerulonephritis; Humans; Male; Medical sciences; Mutation; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Pedigree; Polymorphism, Single-Stranded Conformational; Potassium Channels - chemistry; Potassium Channels - genetics; Potassium Channels, Inwardly Rectifying; Sodium-Potassium-Chloride Symporters; Endocrinopathy; Human; Urinary system disease; Adrenal cortex diseases; Hyperaldosteronism; Renal disease; Hyperadrenocorticism; Ionic channel; Genetic disease; Bartter syndrome; Heterogeneity; Gene; Adrenal gland diseases; Genetics; Mutation; Potassium
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng1096-152

Mutations in the Na-K-2Cl cotransporter (NKCC2), a mediator of renal salt reabsorption, cause Bartter's syndrome, featuring salt wasting, hypokalaemic alkalosis, hypercalciuria and low blood pressure. NKCC2 mutations can be excluded in some Bartter's kindreds, prompting examination of regulators of cotransporter activity. One regulator is believed to be ROMK, an ATP-sensitive K+ channel that 'recycles' reabsorbed K+ back to the tubule lumen. Examination of the ROMK gene reveals mutations that co-segregate with the disease and disrupt ROMK function in four Bartter's kindreds. Our findings establish the genetic heterogeneity of Bartter's syndrome, and demonstrate the physiologic role of ROMK in vivo.