title: A syndrome of congenital hyperinsulinism and rhabdomyolysis is caused by KCNJ11 mutation.
abstract: BACKGROUND
  Congenital hyperinsulinism is a genetically heterogeneous disorder, but mutations in the components of the ATP-sensitive potassium channel K(ATP) account for more than a third of all isolated congenital hyperinsulinism cases. The association between congenital hyperinsulinism and rhabdomyolysis has not been reported.
  
  
  OBJECTIVE
  To describe significant skeletal muscle manifestations in a family with a novel mutation in KCNJ11 (encoding the Kir6.2 component of K(ATP)).
  
  
  METHODS
  Cross-sectional analysis of members of a large multiplex consanguineous family with congenital hyperinsulinism and rhabdomyolysis using autozygosity mapping and exome sequencing.
  
  
  RESULTS
  Five affected members of an extended consanguineous Saudi family were recruited along with relevant unaffected relatives. We were able to map an apparently novel syndrome of congenital hyperinsulinism and severe rhabdomyolysis leading to acute renal failure to a single locus that harbours KCNJ11 in which we identified a novel homozygous mutation.
  
  
  CONCLUSIONS
  This study expands the phenotype associated with KCNJ11 loss of function in humans and calls for increased awareness of rhabdomyolysis as a potential late-onset life-threatening complication of KCNJ11-related congenital hyperinsulinism.
authors.affiliation: Division of Nephrology, Department of Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Albaqumi
authors.forename: Fatimah A
authors.initials: FA
authors.lastname: Alhabib
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.forename: Firdous
authors.initials: F
authors.lastname: Mohammed
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D001483:Base Sequence; D044903:Congenital Hyperinsulinism / Q000150:complications* / Q000235:genetics*; D005190:Family; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012206:Rhabdomyolysis / Q000150:complications* / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel
keywords: Calcium; Kir6.2; Renal Failure; Rhabdomyolysis