TY - JOUR
T1 - 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
AU - Syrén, Marie Louise
AU - Borsa Ghiringhelli, Nicol
AU - Bettinelli, Alberto
AU - Colussi, Giacomo
AU - Vargas-Poussou, Rosa
AU - Tammaro, Fabiana
AU - Coviello, Domenico A.
AU - Tedeschi, Silvana
PY - 2011/2
Y1 - 2011/2
N2 - 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.
AB - 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.
KW - common ancestor
KW - Gitelman's syndrome
KW - population-specific mutation
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U2 - 10.1093/ndt/gfq458
DO - 10.1093/ndt/gfq458
M3 - Article
C2 - 20675610
AN - SCOPUS:79551503913
VL - 26
SP - 557
EP - 561
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
SN - 0931-0509
IS - 2
ER -