Pediatric Nephrology

, Volume 10, Issue 4, pp 403–407

Linkage of Gitelman syndrome to the thiazide-sensitive sodium-chloride cotransporter gene with identification of mutations in Dutch families

Authors

  • Henny H. Lemmink
    • Department of Pediatrics, University of Nijmegen, Nijmegen, The Netherlands
  • Lambert P. W. J. van den Heuvel
    • Department of Pediatrics, University of Nijmegen, Nijmegen, The Netherlands
  • Henk A. van Dijk
    • Department of Pediatrics, University of Nijmegen, Nijmegen, The Netherlands
  • Gerard F. M. Merkx
    • Department of Human Genetics, University of Nijmegen, Nijmegen, The Netherlands
  • Tineke J. Smilde
    • Department of Internal Medicine, University of Nijmegen, Nijmegen, The Netherlands
  • Peter E. M. Taschner
    • Department of Human Genetics, University of Leiden, Leiden, The Netherlands
  • Leo A. H. Monnens
    • Department of Pediatrics, University of Nijmegen, Nijmegen, The Netherlands
  • Steve C. Hebert
    • Harvard Center for Study of Kidney Diseases, Brigham and Women’s Hospital, Boston, USA
  • Nine V. A. M. Knoers
    • Department of Human Genetics, University of Nijmegen, Nijmegen, The Netherlands
Original article

DOI: 10.1007/s004670050129

Cite this article as:
Lemmink, H., van den Heuvel, L., van Dijk, H. et al. Pediatr Nephrol (1996) 10: 403. doi:10.1007/s004670050129

Abstract.

Gitelman syndrome is a mostly autosomal recessive disorder affecting the renal tubular function associated with hypokalemia and hypomagnesemia. Functional studies point to a defect in the distal renal tubule in the thiazide-sensitive, electroneutral sodium-chloride cotransporter (TSC). Based upon the localization of a 2.6 cDNA encoding the human TSC to chromosome 16q13, polymorphic markers spanning the region from 16p12 to 16q21 were tested for linkage to the Gitelman syndrome locus in three Dutch families with autosomal recessive inheritance of this disorder. Using two-point linkage analysis, a maximum LOD score (Zmax of 4.49 (at Θ = 0.00) was found for the marker D16S408. One crucial recombination event places the Gitelman syndrome locus distal to D16S419 at 16q12-13. Subsequently we have tested our group of Gitelman patients for mutations in the human TSC gene. Two mutations were identified in three Gitelman families. Our study confirms that the human TSC gene is involved in Gitelman syndrome. Patients from three Gitelman families reveal two identical human TSC mutations, suggesting these families share a common ancestor.

Key words: Autosomal recessive Gitelman syndromeThiazide-sensitive sodium-chloride cotransporterLinkage analysisMutation analysis

Copyright information

© International Pediatric Nephrology Association New York, USA 1996