Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy
© 2013 Wiley Periodicals, Inc..
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Clinical and translational science - 6(2013), 6 vom: 12. Dez., Seite 424-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Merlo, Marco [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.08.2014 Date Revised 11.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cts.12116 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM231636180 |
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| 245 | 1 | 0 | |a Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy |
| 264 | 1 | |c 2013 | |
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| 500 | |a Date Completed 11.08.2014 | ||
| 500 | |a Date Revised 11.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2013 Wiley Periodicals, Inc. | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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) | ||
| 520 | |a CONCLUSIONS: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Multicenter Study | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a cardiomyopathy | |
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| 700 | 1 | |a Carniel, Elisa |e verfasserin |4 aut | |
| 700 | 1 | |a Slavov, Dobromir |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiao |e verfasserin |4 aut | |
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| 700 | 1 | |a Spezzacatene, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Ramani, Federica |e verfasserin |4 aut | |
| 700 | 1 | |a Salcedo, Ernesto |e verfasserin |4 aut | |
| 700 | 1 | |a Di Lenarda, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Mestroni, Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Matthew R G |e verfasserin |4 aut | |
| 700 | 0 | |a Familial Cardiomyopathy Registry |e verfasserin |4 aut | |
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