title: Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients.
abstract: BACKGROUND
  The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands.
  
  
  RESULTS
  We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On beta blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2-37) years.
  
  
  CONCLUSIONS
  CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with beta blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of beta blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies.
authors.forename: A V
authors.initials: AV
authors.lastname: Postma
authors.forename: I
authors.initials: I
authors.lastname: Denjoy
authors.forename: J
authors.initials: J
authors.lastname: Kamblock
authors.forename: M
authors.initials: M
authors.lastname: Alders
authors.forename: J-M
authors.initials: JM
authors.lastname: Lupoglazoff
authors.forename: G
authors.initials: G
authors.lastname: Vaksmann
authors.forename: L
authors.initials: L
authors.lastname: Dubosq-Bidot
authors.forename: P
authors.initials: P
authors.lastname: Sebillon
authors.forename: M M A M
authors.initials: MM
authors.lastname: Mannens
authors.forename: P
authors.initials: P
authors.lastname: Guicheney
authors.forename: A A M
authors.initials: AA
authors.lastname: Wilde
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D001919:Bradycardia / Q000235:genetics*; D002395:Catecholamines / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013575:Syncope / Q000235:genetics; D013610:Tachycardia / Q000235:genetics; D017180:Tachycardia, Ventricular / Q000235:genetics*
chemical_list: D002395:Catecholamines; D019837:Ryanodine Receptor Calcium Release Channel