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Article Dans Une Revue Journal of the American Society of Nephrology Année : 2011

Spectrum of mutations in Gitelman syndrome.

Rosa Vargas-Poussou
Karin Dahan
  • Fonction : Auteur
Diana Kahila
  • Fonction : Auteur
Annabelle Venisse
  • Fonction : Auteur
Eva Riveira-Munoz
  • Fonction : Auteur
Huguette Debaix
  • Fonction : Auteur
Bernard Grisart
  • Fonction : Auteur
Robert Unwin
Bruno Moulin
  • Fonction : Auteur
Jean-Philippe Haymann
  • Fonction : Auteur
  • PersonId : 956379
Marie-Christine Vantyghem
  • Fonction : Auteur
Claire Rigothier
  • Fonction : Auteur
Bertrand Dussol
  • Fonction : Auteur
Michel Godin
  • Fonction : Auteur
Hubert Nivet
  • Fonction : Auteur
Laurence Dubourg
  • Fonction : Auteur
Ivan Tack
  • Fonction : Auteur
Anne-Paule Gimenez-Roqueplo
Pascal Houillier
Anne Blanchard

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-00945691 , version 1 (12-02-2014)

Identifiants

Citer

Rosa Vargas-Poussou, Karin Dahan, Diana Kahila, Annabelle Venisse, Eva Riveira-Munoz, et al.. Spectrum of mutations in Gitelman syndrome.. Journal of the American Society of Nephrology, 2011, 22 (4), pp.693-703. ⟨10.1681/ASN.2010090907⟩. ⟨hal-00945691⟩
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