A new SLC12A3 founder mutation (p.Val647Met) in Gitelman's syndrome patients of Roma ancestry.

Autor:	Gil-Peña H; Dept. Pediatría-RENALTUBE Consortium, Hospital Universitario Central Asturias, Oviedo, Spain. Electronic address: hgilpena@gmail.com., Coto E; Dept. Genética Molecular-Red de Investigación Renal, Hospital Universitario Central Asturias, Oviedo, Spain; Hôpital Européen Georges Pompidou, France., Santos F; Dept. Pediatría-RENALTUBE Consortium, Hospital Universitario Central Asturias, Oviedo, Spain; Hôpital Européen Georges Pompidou, France., Espino M; Hospital Doce de Octubre, Madrid, Spain., Cea Crespo JM; Hospital Severo Ochoa, Leganés, Spain., Chantzopoulos G; Dept. Pediatrics, Aghia Sophia Children's Hospital, Athens, Greece., Komianou F; Dept. Pediatrics, Aghia Sophia Children's Hospital, Athens, Greece., Gómez J; Dept. Genética Molecular-Red de Investigación Renal, Hospital Universitario Central Asturias, Oviedo, Spain., Alonso B; Dept. Genética Molecular-Red de Investigación Renal, Hospital Universitario Central Asturias, Oviedo, Spain., Iglesias S; Dept. Genética Molecular-Red de Investigación Renal, Hospital Universitario Central Asturias, Oviedo, Spain., Treard C; Hôpital Européen Georges Pompidou, France., Vargas-Poussou R; Hôpital Européen Georges Pompidou, France.
Jazyk:	English; Spanish; Castilian
Zdroj:	Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia [Nefrologia] 2017 Jul - Aug; Vol. 37 (4), pp. 423-428. Date of Electronic Publication: 2017 Mar 18.
DOI:	10.1016/j.nefro.2017.01.007
Abstrakt:	Background: Gitelman'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. Objectives: To characterize a second SLC12A3 mutation in Roma patients negative for the intron 9 variant. Methods: SLC12A3 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. Results: We 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. Conclusion: We 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. (Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)
Databáze:	MEDLINE
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