Poor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy
Article first published online: 3 OCT 2013
© 2013 Wiley Periodicals, Inc.
Clinical and Translational Science
Volume 6, Issue 6, pages 424–428, December 2013
How to Cite
Merlo, M., Sinagra, G., Carniel, E., Slavov, D., Zhu, X., Barbati, G., Spezzacatene, A., Ramani, F., Salcedo, E., Di Lenarda, A., Mestroni, L., Taylor, M. R. G. (2013), Poor Prognosis of Rare Sarcomeric Gene Variants in Patients with Dilated Cardiomyopathy. Clinical and Translational Science, 6: 424–428. doi: 10.1111/cts.12116
- Issue published online: 13 DEC 2013
- Article first published online: 3 OCT 2013
- NIH. Grant Numbers: UL1 RR025780, RO1 HL69071, K23 JL067915, 1R01HL109209-01A1
- molecular genetics;
In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry.
DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN were identified. Genotype–phenotype association analysis was performed, and long-term survival-free from death or heart transplant was compared between carriers and noncarriers.
We found 24 rare variants (3 in MYH6, 3 in MYH7, 3 in MYBPC3, 2 in TNNT2, and 13 in TTN) affecting 52 subjects in 25 families. The phenotypes of variant carriers were severe (3 sudden deaths, 6 heart failure deaths, 8 heart transplants, 2 ventricular fibrillations). There was no difference in the overall long-term survival between carriers and the 33 noncarriers (p = 0.322). However after 50 years of age, the combined endpoint of death or transplant was decreased in carriers as compared to noncarriers (p = 0.026).
Patients with DCM carrying rare variants in sarcomeric genes manifest a poorer prognosis as compared to noncarriers after the age of 50 years. These data further support the role of genetic testing in DCM for risk stratification.