title: A new mutation (intron 9 +1 G>T) in the SLC12A3 gene is linked to Gitelman syndrome in Gypsies.
abstract: BACKGROUND
  Gitel syndrome is an inherited tubular disorder characterized by metabolic alkalosis, hypokalemia, and hypomagnesemia of renal origin and hypocalciuria. The majority of patients with Gitelman syndrome carry inactivating mutations in the SLC12A3 gene encoding the sodium-chloride cotransporter located in the distal convoluted tubule. The purpose of this study was to investigate the underlying mutation in Gitelman syndrome patients of Gypsy race from different geographic origin.
  
  
  METHODS
  Twenty Gypsy patients with clinical and biochemical features of Gitelman syndrome were investigated by mutational analysis. The patients belonged to 12 unrelated Gypsy families living in four different European countries. The parents and unaffected siblings of each patient, as well as the DNA of a population of 200 healthy control patients, were also analyzed.
  
  
  RESULTS
  All patients were homozygous for the same splice site mutation, guanine to thymine in the first position of intron 9 of SLC12A3 gene. This mutation was not found in the control population. Parents were heterozygous for the mutation. Despite sharing a common mutation, the clinical manifestations of the syndrome in the patients varied from lack of symptoms in six children to severe growth retardation in four.
  
  
  CONCLUSIONS
  Demonstration of a novel point mutation within the SLC12A3 gene in our cohort of Gypsy families with Gitelman syndrome is highly suggestive of a founder effect. This finding will facilitate the identification of the genetic defect in further cases of Gitelman syndrome among the Gypsy population. Our study represents the largest series ever published of patients with Gitelman syndrome having the same underlying mutation, and supports the lack of correlation between genotype and clinical phenotype in this disease.
authors.affiliation: Hospital Universitario Central de Asturias, Spain.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
authors.forename: Julian
authors.initials: J
authors.lastname: Rodriguez
authors.forename: Nikola
authors.initials: N
authors.lastname: Jeck
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Rosario
authors.initials: R
authors.lastname: Stone
authors.forename: Cesar
authors.initials: C
authors.lastname: Loris
authors.forename: Luis M
authors.initials: LM
authors.lastname: Rodriguez
authors.forename: Michel
authors.initials: M
authors.lastname: Fischbach
authors.forename: Hannsjörg W
authors.initials: HW
authors.lastname: Seyberth
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000471:Alkalosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018703:Founder Effect; D005838:Genotype; D006801:Humans; D007008:Hypokalemia / Q000235:genetics*; D007223:Infant; D007438:Introns / Q000235:genetics; D007674:Kidney Diseases / Q000235:genetics*; D008275:Magnesium Deficiency / Q000235:genetics; D008297:Male; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D011955:Receptors, Drug / Q000235:genetics*; D006178:Romani People / Q000235:genetics*; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters
chemical_list: D002352:Carrier Proteins; D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor