12
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Spectrum of mutations in Gitelman syndrome.

      Journal of the American Society of Nephrology : JASN
      Adolescent, Adult, Alleles, Base Sequence, Child, Child, Preschool, Chloride Channels, genetics, Female, Gene Dosage, Gene Rearrangement, Genetic Predisposition to Disease, Genetic Testing, Gitelman Syndrome, Humans, Male, Middle Aged, Molecular Sequence Data, Mutation, Receptors, Drug, Retrospective Studies, Sensitivity and Specificity, Solute Carrier Family 12, Member 3, Symporters, Young Adult

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene. Copyright © 2011 by the American Society of Nephrology

          Related collections

          Author and article information

          Comments

          Comment on this article