Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter

David B. Simon, Carol Nelson-Williams, Margaret Johnson Bia, David Ellison, Fiona E. Karet, Antonio Morey Molina, Ivar Vaara, Fujihiko Iwata, Howard M. Cushner, Marianne Koolen, Francisco J. Gainza, Hillel J. Gitelman, Richard P. Lifton

Research output: Contribution to journalArticle

917 Citations (Scopus)

Abstract

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartter's syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelman's syndrome to the locus encoding the renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelman's syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

Original languageEnglish (US)
Pages (from-to)24-30
Number of pages7
JournalNature Genetics
Volume12
Issue number1
DOIs
StatePublished - Jan 1996
Externally publishedYes

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Gitelman Syndrome
Bartter Syndrome
Alkalosis
Mutation
Electrolytes
Homeostasis
Alleles
Heterozygote
Sodium Chloride
Maintenance
Hypertension
Kidney
thiazide receptor

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. / Simon, David B.; Nelson-Williams, Carol; Bia, Margaret Johnson; Ellison, David; Karet, Fiona E.; Molina, Antonio Morey; Vaara, Ivar; Iwata, Fujihiko; Cushner, Howard M.; Koolen, Marianne; Gainza, Francisco J.; Gitelman, Hillel J.; Lifton, Richard P.

In: Nature Genetics, Vol. 12, No. 1, 01.1996, p. 24-30.

Research output: Contribution to journalArticle

Simon, DB, Nelson-Williams, C, Bia, MJ, Ellison, D, Karet, FE, Molina, AM, Vaara, I, Iwata, F, Cushner, HM, Koolen, M, Gainza, FJ, Gitelman, HJ & Lifton, RP 1996, 'Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter', Nature Genetics, vol. 12, no. 1, pp. 24-30. https://doi.org/10.1038/ng0196-24
Simon, David B. ; Nelson-Williams, Carol ; Bia, Margaret Johnson ; Ellison, David ; Karet, Fiona E. ; Molina, Antonio Morey ; Vaara, Ivar ; Iwata, Fujihiko ; Cushner, Howard M. ; Koolen, Marianne ; Gainza, Francisco J. ; Gitelman, Hillel J. ; Lifton, Richard P. / Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. In: Nature Genetics. 1996 ; Vol. 12, No. 1. pp. 24-30.
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