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Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na–K–2CI cotransporter NKCC2

Nature Genetics volume 13, pages 183–188 (1996)Cite this article

Abstract

Inherited hypokalaemic alkalosis with low blood pressure can be divided into two groups — Gitelman's syndrome, featuring hypocalciuria, hypomagnesaemia and milder clinical manifestations, and Bartter's syndrome, featuring hypercalciuria and early presentation with severe volume depletion. Mutations in the renal Na–Cl cotransporter have been shown to cause Gitelman's syndrome. We demonstrate linkage of Bartter's syndrome to the renal Na–K–2Cl cotransporter gene NKCC2, and identify frameshift or non–conservative missense mutations for this gene that co–segregate with the disease. These findings demonstrate the molecular basis of Bartter's syndrome, provide the basis for molecular classification of patients with inherited hypokalaemic alkalosis, and suggest potential phenotypes in heterozygous carriers of NKCC2 mutations.

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Author notes

  1. David B. Simon and Fiona E. Karet: D.B.S. & F.E.K. contributed equally to this work.

Authors and Affiliations

  1. Howard Hughes Medical Institute, Departments of Medicine and Genetics, Boyer Center/or Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut, 06510, USA

    David B. Simon, Fiona E. Karet & Richard P. Lifton

  2. Specialty Pediatric Services Division, Dharan Health Center, Room A-406, Box 76, Dharan, 31311, Saudi Arabia

    Jahed M. Hamdan

  3. OspedaleA. Cardarelli, 28 Div. Pediatria, Via A, Cardarelli no.9, 80131, Napoli, Italy

    Antonio Di Pietro

  4. Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Sami A. Sanjad

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  1. David B. Simon
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Simon, D., Karet, F., Hamdan, J. et al. Bartter's syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na–K–2CI cotransporter NKCC2. Nat Genet 13, 183–188 (1996). https://doi.org/10.1038/ng0696-183

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