title: 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.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dipartimento di Scienze Materno-Infantili, Universita degli Studi di Milano, Laboratorio di Genetica Medica, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy. eva.syren@unimi.it
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Syrén
authors.forename: Nicolò
authors.initials: N
authors.lastname: Borsa Ghiringhelli
authors.forename: Alberto
authors.initials: A
authors.lastname: Bettinelli
authors.forename: Giacomo
authors.initials: G
authors.lastname: Colussi
authors.forename: Rosa
authors.initials: R
authors.lastname: Vargas-Poussou
authors.forename: Fabiana
authors.initials: F
authors.lastname: Tammaro
authors.forename: Domenico A
authors.initials: DA
authors.lastname: Coviello
authors.forename: Silvana
authors.initials: S
authors.lastname: Tedeschi
mesh_terms: D005190:Family; D005260:Female; D016368:Frameshift Mutation; D005602:France; D053579:Gitelman Syndrome / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008297:Male; D005810:Multigene Family; D011110:Polymorphism, Genetic; D011955:Receptors, Drug / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters