title: A novel variant in the SLC12A1 gene in two families with antenatal Bartter syndrome.
abstract: OBJECTIVE
  Bartter syndrome is an autosomal-recessive inherited disease in which patients present with hypokalaemia and metabolic alkalosis. We present two apparently nonrelated cases with antenatal Bartter syndrome type I, due to a novel variant in the SLC12A1 gene encoding the bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2 in the thick ascending limb of the loop of Henle.
  
  
  METHODS
  Blood samples were received from the two cases and 19 of their relatives, and deoxyribonucleic acid was extracted. The coding regions of the SLC12A1 gene were amplified using polymerase chain reaction, followed by bidirectional direct deoxyribonucleic acid sequencing.
  
  
  RESULTS
  Each affected child in the two families was homozygous for a novel inherited variant in the SLC12A1gene, c.1614T>A. The variant predicts a change from a tyrosine codon to a stop codon (p.Tyr538Ter). The two cases presented antenatally and at six months of age, respectively.
  
  
  CONCLUSIONS
  The two cases were homozygous for the same variant in the SLC12A1 gene, but presented clinically at different ages. This could eventually be explained by the presence of other gene variants or environmental factors modifying the phenotypes. The phenotypes of the patients were similar to other patients with antenatal Bartter syndrome.
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Breinbjerg
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Siggaard Rittig
authors.affiliation: Research Unit for Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Gregersen
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Søren
authors.initials: S
authors.lastname: Rittig
authors.affiliation: Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.|Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jane
authors.initials: J
authors.lastname: Hvarregaard Christensen
mesh_terms: D001477:Bartter Syndrome / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011247:Pregnancy; D011296:Prenatal Diagnosis; D064466:Solute Carrier Family 12, Member 1 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C578714:SLC12A1 protein, human; D064466:Solute Carrier Family 12, Member 1
keywords: Bartter syndrome; Hypokalaemic alkalosis; Polyuria; SLC12A1 gene