title: Sudden death associated with QT interval prolongation and KCNQ1 gene mutation in a family of English Springer Spaniels.
abstract: BACKGROUND
  A 5-year-old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly.
  
  
  OBJECTIVE
  Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family.
  
  
  METHODS
  Four remaining dogs from the affected litter and 11 related dogs.
  
  
  METHODS
  Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs.
  
  
  RESULTS
  Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T-wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure.
  
  
  CONCLUSIONS
  This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.
authors.affiliation: Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA.
authors.forename: W A
authors.initials: WA
authors.lastname: Ware
authors.forename: Y
authors.initials: Y
authors.lastname: Reina-Doreste
authors.forename: J A
authors.initials: JA
authors.lastname: Stern
authors.forename: K M
authors.initials: KM
authors.lastname: Meurs
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000662:veterinary*; D016022:Case-Control Studies; D003645:Death, Sudden / Q000662:veterinary*; D004283:Dog Diseases / Q000235:genetics* / Q000503:physiopathology; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D051657:KCNQ1 Potassium Channel
keywords: Long QT Syndrome