title: Phenotype-genotype correlation in antenatal and neonatal variants of Bartter syndrome.
abstract: BACKGROUND
  Ante/neonatal Bartter syndrome (BS) is a hereditary salt-losing tubulopathy due to mutations in genes encoding proteins involved in NaCl reabsorption in the thick ascending limb of Henle's loop. Our aim was to study the frequency, clinical characteristics and outcome of each genetic subtype.
  
  
  METHODS
  Charts of 42 children with mutations in KCNJ1 (n = 19), SLC12A1 (n = 13) CLCNKB (n = 6) or BSND (n = 4) were retrospectively analysed. The median follow-up was 8.3 [0.4-18.0] years.
  
  
  RESULTS
  We describe 24 new mutations: 10 in KCNJ1, 11 in SLC12A1 and 3 in CLCNKB. The onset of polyhydramnios, birth term, height and weight were similar for all groups; three patients had no history of polyhydramnios or premature birth and had CLCNKB mutations according to a less severe renal sodium wasting. Contrasting with these data, patients with CLCNKB had the lowest potassium (P = 0.006 versus KCNJ1 and P = 0.034 versus SLC12A1) and chloride plasma concentrations (P = 0.039 versus KCNJ1 and P = 0.024 versus SLC12A1) and the highest bicarbonataemia (P = 0.026 versus KCNJ1 and P = 0.014 versus SLC12A1). Deafness at diagnosis was constant in patients with BSND mutations; transient neonatal hyperkalaemia was present in two-thirds of the children with KCNJ1 mutations. Nephrocalcinosis was constant in KCNJ1 and SLC12A1 but not in BSND and CLCNKB patients. In most cases, water/electrolyte supplementation + indomethacin led to catch-up growth. Three patients developed chronic renal failure: one with KCNJ1 mutations during the second decade of age and two with CLCNKB and BSND mutations and without nephrocalcinosis during the first year of life.
  
  
  CONCLUSIONS
  We confirmed in a large cohort of ante/ neonatal BS that deafness, transient hyperkalaemia and severe hypokalaemic hypochloraemic alkalosis orientate molecular investigations to BSND, KCNJ1 and CLCNKB genes, respectively. Chronic renal failure is a rare event, associated in this cohort with three genotypes and not always associated with nephrocalcinosis.
authors.affiliation: Hôpitaux de Toulouse, Université Paul Sabathier, Département de Pédiatrie, Centre de Référence des Maladies Rénales Rares, Toulouse F31000, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Brochard
authors.forename: Olivia
authors.initials: O
authors.lastname: Boyer
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Chantal
authors.initials: C
authors.lastname: Loirat
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.forename: Marie-Alice
authors.initials: MA
authors.lastname: Macher
authors.forename: Georges
authors.initials: G
authors.lastname: Deschenes
authors.forename: Albert
authors.initials: A
authors.lastname: Bensman
authors.forename: Stéphane
authors.initials: S
authors.lastname: Decramer
authors.forename: Pierre
authors.initials: P
authors.lastname: Cochat
authors.forename: Denis
authors.initials: D
authors.lastname: Morin
authors.forename: Françoise
authors.initials: F
authors.lastname: Broux
authors.forename: Mathilde
authors.initials: M
authors.lastname: Caillez
authors.forename: Claude
authors.initials: C
authors.lastname: Guyot
authors.forename: Robert
authors.initials: R
authors.lastname: Novo
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaître
authors.forename: Rosa
authors.initials: R
authors.lastname: Vargas-Poussou
mesh_terms: D000293:Adolescent; D000350:Africa, Central; D000352:Africa, Northern; D001477:Bartter Syndrome / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D003638:Deafness / Q000208:ethnology / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006947:Hyperkalemia / Q000208:ethnology / Q000235:genetics; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D009397:Nephrocalcinosis / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012189:Retrospective Studies; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics*; D064466:Solute Carrier Family 12, Member 1; D014421:Turkey; D044465:White People / Q000208:ethnology / Q000235:genetics
chemical_list: C440005:BSND protein, human; C412733:CLCNKB protein, human; D018118:Chloride Channels; C086989:KCNJ1 protein, human; D024661:Potassium Channels, Inwardly Rectifying; C578714:SLC12A1 protein, human; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1