Gitelman's syndrome (Bartter's variant) maps to the thiazide-sensitive cotransporter gene locus on chromosome 16q13 in a large kindred.
A defect in distal renal tubular sodium chloride handling is thought to be responsible for the clinical phenotype of Gitelman's syndrome, a variant of Bartter's syndrome. To study the possible involvement of the renal thiazide-sensitive NaCl cotransporter gene in the syndrome, a linkage analysis study in the largest reported kindred with the syndrome was performed. A human homolog of rat thiazide-sensitive cotransporter was cloned and mapped to chromosome 16q13 by fluorescent in situ hybridization. All 17 family members in two generations were genotyped at loci in this region. There were no recombinants observed between the Gitelman's syndrome phenotype and inheritance of D16S408 alleles, yielding a lod score of 3.88 at Q = 0. By contrast, recombinants were observed between Gitelman's syndrome and the flanking markers D16S419 and D16S400, localizing the responsible gene in this family to a 15 centimorgan region on chromosome 16q. These genetic data, together with current understanding of the molecular physiology of the thiazide-sensitive cotransporter, are strong evidence that the latter is defective in this kindred with Gitelman's syndrome.
Pollak
M R
MR
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Delaney
V B
VB
Graham
R M
RM
Hebert
S C
SC
D000328:Adult; D001477:Bartter Syndrome / Q000235:genetics* / Q000503:physiopathology; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D008040:Genetic Linkage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008126:Lod Score; D008969:Molecular Sequence Data; D010375:Pedigree; D011955:Receptors, Drug / Q000235:genetics*; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
D002352:Carrier Proteins; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor