Cui Hao, Wang Jizheng, Zhang Ce, Wu Guixin, Zhu Changsheng, Tang Bing, Zou Yubao, Huang Xiaohong, Hui Rutai, Song Lei, Wang Shuiyun
Department of Cardiac Surgery, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
State Key Laboratory of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mol Genet Genomic Med. 2018 Nov;6(6):1104-1113. doi: 10.1002/mgg3.488. Epub 2018 Nov 8.
Filamin C (FLNC) mutation was reported as a cause of HCM, with a high probability of sudden cardiac death. However, the mutation profile of FLNC, and its relationship with phenotypic expression in HCM, remains to be elucidated.
In this study, FLNC gene was sequenced in 540 HCM patients and 307 healthy controls.
We found that 39 (7.2%) patients carried FLNC mutations, with a similar frequency to that of controls (4.2%, p = 0.101). Pedigree analysis showed that mutations were not well segregated with HCM. The baseline characteristics between HCM patients, with and without mutations, were comparable. FLNC mutations did not increase the risk for either all-cause mortality (HR 0.746, 95% CI 0.222-2.295, p = 0.575) or cardiac mortality (HR 0.615, 95% CI 0.153-1.947, p = 0.354) in HCM patients during a follow-up of 4.7 ± 3.2 years. Moreover, there was no significant difference in survival free from sudden cardiac arrest (HR 0.721, 95% CI 0.128-3.667, p = 0.660) and heart failure (HR 0.757, 95% CI 0.318-1.642, p = 0.447).
FLNC mutations were common in both HCM patients and healthy population. The pathogenicity of FLNC mutations detected in HCM patients and its association with the clinical outcomes should be cautiously interpreted.
据报道，细丝蛋白C（FLNC）突变是肥厚型心肌病（HCM）的一个病因，具有较高的心源性猝死概率。然而，FLNC的突变谱及其与HCM表型表达的关系仍有待阐明。
在本研究中，对540例HCM患者和307例健康对照者进行了FLNC基因测序。
我们发现39例（7.2%）患者携带FLNC突变，其频率与对照组相似（4.2%，p = 0.101）。家系分析表明，突变与HCM的分离情况不佳。有突变和无突变的HCM患者的基线特征具有可比性。在4.7±3.2年的随访期间，FLNC突变并未增加HCM患者全因死亡率（风险比[HR]0.746，95%置信区间[CI]0.222 - 2.295，p = 0.575）或心源性死亡率（HR 0.615，95% CI 0.153 - 1.947，p = 0.354）的风险。此外，在无心脏骤停（HR 0.721，95% CI 0.128 - 3.667，p = 0.660）和心力衰竭（HR 0.757，95% CI 0.318 - 1.642，p = 0.447）的生存率方面无显著差异。
FLNC突变在HCM患者和健康人群中均很常见。对于在HCM患者中检测到的FLNC突变的致病性及其与临床结局的关联应谨慎解读。
