TY - JOUR T1 - A new SLC12A3 founder mutation (p.Val647Met) in Gitelman's syndrome patients of Roma ancestry JO - Nefrología T2 - AU - Gil-Peña,Helena AU - Coto,Eliecer AU - Santos,Fernando AU - Espino,Mar AU - Cea Crespo,Jose Mª AU - Chantzopoulos,Giannis AU - Komianou,Filadelfia AU - Gómez,Juan AU - Alonso,Belén AU - Iglesias,Sara AU - Treard,Cyrielle AU - Vargas-Poussou,Rosa SN - 02116995 M3 - 10.1016/j.nefro.2017.01.007 DO - 10.1016/j.nefro.2017.01.007 UR - https://revistanefrologia.com/es-a-new-slc12a3-founder-mutation-articulo-S0211699517300449 AB - BackgroundGitelman's syndrome (GS) is an autosomal recessive disorder caused by mutations in the SLC12A3 gene. GS is characterized by hypokalaemic metabolic alkalosis, hypomagnesemia and hypocalciuria. Most of the reported patients of Roma ancestry are homozygous for an SLC12A3 intron 9 frameshifting mutation (c.1180+1G>T). Some forms of Bartter's syndrome result from mutations in the CLNCKB gene and clinically overlap with GS. ObjectivesTo characterize a second SLC12A3 mutation in Roma patients negative for the intron 9 variant. MethodsSLC12A3 and CLNCKB genes were analyzed by next-generation sequencing in two Spanish and Greek gypsy patients who were negative for the intron 9 splicing mutation. Sanger sequencing was performed to confirm the putative mutations in patients and family members. ResultsWe identified a missense variant (p.Val647Met, c.1939G>A) in both cases, and both were homozygous for Met. This mutation was also found in three additional patients; two homozygous and one heterozygous compound with the intron 9 splicing mutation. This new SLC12A3 mutation seems to be characteristic of gipsy GS patients and was linked to the same haplotype in all cases, supporting a founder origin. All the patients showed biochemical features characteristic of GS. ConclusionWe report a second founder mutation among GS patients of Roma ethnic background. The direct screening of this mutation would facilitate the characterization of patients who are negative for the more common intron 9 +1G>T mutation. ER -