Cardiovascular Institute and Adult Medical Genetics, University of Colorado, Aurora, Colorado, USA; Cardiovascular Department "Ospedali Riuniti,"and University of Trieste, Trieste, Italy.
Clin Transl Sci. 2013 Dec;6(6):424-8. doi: 10.1111/cts.12116. Epub 2013 Oct 3.
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.
在扩张型心肌病（DCM）中，肌节基因罕见变异的临床和预后意义仍知之甚少。为了解决这个问题，我们分析了我们家族性心肌病登记处中患有罕见肌节基因变异的患者的结局。
鉴定出 MYH6、MYH7、MYBPC3、TNNT2 和 TTN 中存在罕见肌节变异的 DCM 家族。进行基因型-表型关联分析，并比较携带者和非携带者的长期生存情况（免于死亡或心脏移植）。
我们发现 24 个罕见变异（3 个在 MYH6 中，3 个在 MYH7 中，3 个在 MYBPC3 中，2 个在 TNNT2 中，13 个在 TTN 中）影响了 25 个家族中的 52 个受试者。变异携带者的表型严重（3 例猝死，6 例心力衰竭死亡，8 例心脏移植，2 例心室颤动）。携带者和 33 名非携带者之间的总体长期生存没有差异（p = 0.322）。然而，50 岁以后，与非携带者相比，携带者的死亡或移植联合终点减少（p = 0.026）。
与非携带者相比，携带肌节基因罕见变异的 DCM 患者在 50 岁以后预后较差。这些数据进一步支持在 DCM 中进行基因检测以进行风险分层的作用。
