Journal Article

The mutation c.1196_1202dup7bp (p.Ser402X) in the <i>SLC12A3</i> gene clusters in Italian Gitelman syndrome patients and reflects the presence of a common ancestor

Marie-Louise Syrén, Nicolò Borsa Ghiringhelli, Alberto Bettinelli, Giacomo Colussi, Rosa Vargas-Poussou, Fabiana Tammaro, Domenico A. Coviello and Silvana Tedeschi

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 26, issue 2, pages 557-561
Published in print February 2011 | ISSN: 0931-0509
Published online July 2010 | e-ISSN: 1460-2385 | DOI:
The mutation c.1196_1202dup7bp (p.Ser402X) in the SLC12A3 gene clusters in Italian Gitelman syndrome patients and reflects the presence of a common ancestor

Show Summary Details


Background. Inactivating mutations in the SLC12A3 gene are the main cause of Gitelman’s syndrome (GS), a renal tubular disorder inherited as an autosomal recessive trait. In our cohort of patients, we identified 11 probands from 11 apparently unrelated Italian families that carry the c.1196_1202dup7bp mutation, which appears to be more frequent than other mutations in Italian GS patients. Therefore, we characterized in greater detail the SLC12A3 locus and its vicinity in those patients that carry this mutation in order to detect a possible shared haplotype. Three further probands characterized in France, carrying the same mutation, were also included in this study.

Methods. Sequence or fragment analyses were carried out to investigate seven intragenic polymorphisms (rs3217425, rs3816119, rs2304483, rs2278490, rs2278489, rs2289116 and rs2289115) that flank the mutation, as well as two extragenic markers, D16S3071 and D16S3057, flanking the SLC12A3 locus in the 5′ and 3′ termini, respectively.

Results. A shared haplotype co-segregates with the mutation both in Italian and French probands. Moreover, all the Italian families originate from a restricted area of Italy. Likewise, the French probands come from an area of France close to the north of Italy.

Conclusion. It is likely that the c.1196_1202dup7bp mutation in the SLC12A3 gene reflects the presence of a common ancestor in an area covering the northern-central part of Italy and eastern France. A modified genotyping strategy for GS patients originating from this area has to be considered.

Keywords: common ancestor; Gitelman’s syndrome; population-specific mutation

Journal Article.  2787 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.