Abstract | BACKGROUND: METHODS AND 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. CONCLUSION: 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.
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Authors | A V Postma, I Denjoy, J Kamblock, M Alders, J-M Lupoglazoff, G Vaksmann, L Dubosq-Bidot, P Sebillon, M M A M Mannens, P Guicheney, A A M Wilde |
Journal | Journal of medical genetics
(J Med Genet)
Vol. 42
Issue 11
Pg. 863-70
(Nov 2005)
ISSN: 1468-6244 [Electronic] England |
PMID | 16272262
(Publication Type: Letter, Research Support, Non-U.S. Gov't)
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Chemical References |
- Catecholamines
- Ryanodine Receptor Calcium Release Channel
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Topics |
- Adolescent
- Amino Acid Sequence
- Bradycardia
(genetics)
- Catecholamines
(metabolism)
- Child
- Child, Preschool
- Female
- Humans
- Male
- Middle Aged
- Molecular Sequence Data
- Mutation
- Polymorphism, Genetic
- Ryanodine Receptor Calcium Release Channel
(genetics)
- Sequence Homology, Amino Acid
- Syncope
(genetics)
- Tachycardia
(genetics)
- Tachycardia, Ventricular
(genetics)
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