title: Linkage of Gitelman syndrome to the thiazide-sensitive sodium-chloride cotransporter gene with identification of mutations in Dutch families.
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 co-transporter (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 theta = 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.
authors.affiliation: Department of Pediatrics, University of Nijmegen, The Netherlands.
authors.forename: H H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: L P
authors.initials: LP
authors.lastname: van den Heuvel
authors.forename: H A
authors.initials: HA
authors.lastname: van Dijk
authors.forename: G F
authors.initials: GF
authors.lastname: Merkx
authors.forename: T J
authors.initials: TJ
authors.lastname: Smilde
authors.forename: P E
authors.initials: PE
authors.lastname: Taschner
authors.forename: L A
authors.initials: LA
authors.lastname: Monnens
authors.forename: S C
authors.initials: SC
authors.lastname: Hebert
authors.forename: N V
authors.initials: NV
authors.lastname: Knoers
mesh_terms: D001581:Benzothiadiazines; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015342:DNA Probes; D004232:Diuretics; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007008:Hypokalemia / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism / Q000503:physiopathology; D008126:Lod Score; D008274:Magnesium / Q000097:blood / Q000378:metabolism; D009154:Mutation; D009426:Netherlands; D010375:Pedigree; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D049992:Sodium Chloride Symporters; D027981:Symporters; D013577:Syndrome
chemical_list: D001581:Benzothiadiazines; D002352:Carrier Proteins; D015342:DNA Probes; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D049992:Sodium Chloride Symporters; D027981:Symporters; D008274:Magnesium