title: Andersen-Tawil syndrome: new potassium channel mutations and possible phenotypic variation.
abstract: OBJECTIVE
  To evaluate clinical, genetic, and electrophysiologic features of patients with Andersen-Tawil syndrome (ATS) in the United Kingdom.
  
  
  METHODS
  Clinical and neurophysiologic evaluation was conducted of 11 families suspected to have ATS. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control samples were screened by direct DNA sequencing. The electrophysiologic consequences of several new mutations were studied in an oocyte expression system.
  
  
  RESULTS
  All 11 ATS families harbored pathogenic mutations in KCNJ2 with six mutations not previously reported. Some unusual clinical features including renal tubular defect, CNS involvement, and dental and phonation abnormalities were observed. Five mutations (T75M, D78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctional channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect.
  
  
  CONCLUSIONS
  Six new disease-causing mutations in KCNJ2 were identified, one of which was in a PIP2 binding site. Molecular expression studies indicated that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important cause of ATS in the UK.
authors.affiliation: Muscle and Nerve Centre, Queen Elizabeth Hospital, University of Birmingham NHS Trust, UK.
authors.forename: N P
authors.initials: NP
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Imbrici
authors.forename: D
authors.initials: D
authors.lastname: Fialho
authors.forename: C
authors.initials: C
authors.lastname: Herd
authors.forename: L G
authors.initials: LG
authors.lastname: Bilsland
authors.forename: A
authors.initials: A
authors.lastname: Weber
authors.forename: R
authors.initials: R
authors.lastname: Mueller
authors.forename: D
authors.initials: D
authors.lastname: Hilton-Jones
authors.forename: J
authors.initials: J
authors.lastname: Ealing
authors.forename: B R
authors.initials: BR
authors.lastname: Boothman
authors.forename: P
authors.initials: P
authors.lastname: Giunti
authors.forename: L M
authors.initials: LM
authors.lastname: Parsons
authors.forename: M
authors.initials: M
authors.lastname: Thomas
authors.forename: A Y
authors.initials: AY
authors.lastname: Manzur
authors.forename: K
authors.initials: K
authors.lastname: Jurkat-Rott
authors.forename: F
authors.initials: F
authors.lastname: Lehmann-Horn
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: M
authors.initials: M
authors.lastname: Rose
authors.forename: D M
authors.initials: DM
authors.lastname: Kullmann
authors.forename: M G
authors.initials: MG
authors.lastname: Hanna
mesh_terms: D000293:Adolescent; D000328:Adult; D050030:Andersen Syndrome / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D007684:Kidney Tubules / Q000002:abnormalities; D008297:Male; D009154:Mutation / Q000235:genetics*; D009865:Oocytes; D010641:Phenotype; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D014071:Tooth Abnormalities / Q000235:genetics; D014982:Xenopus laevis
chemical_list: C489457:KCNJ2 protein, human; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying