在扩张性心肌病症中,德斯敏突变的患病率
Matthew R G Taylor1, Dobromir Slavov, Lisa Ku
1University of Colorado at Denver and Health Sciences Center, Denver, Colo, USA. Matthew.Taylor@UCHSC.edu
Circulation
|February 28, 2007
概括
德斯敏基因 (DES) 突变在扩张性心肌病 (DCM) 病例的1-2%中被发现,即使没有骨肌疾病. 1A和2B域突变都会导致DCM,有些突变对desmin网络的影响不那么严重.
科学领域:
- 心血管遗传学 心血管遗传学
- 肌肉疾病 肌肉疾病
- 分子生物学分子生物学
背景情况:
- 与desmin相关的肌纤维肌病 (DRM) 是一种遗传性疾病,由于desmin (DES) 基因的突变,影响心脏和骨肌肉.
- 在DES 2B领域的突变通常会在心脏问题之前引起骨肌肉问题.
- 在没有先前骨肌疾病的扩张性心肌病 (DCM) 患者中,DES突变的发生频率仍然未被表征.
研究的目的:
- 确定在被诊断为DCM的个体中DES突变的流行率.
- 研究新型DES突变对心脏细胞中desmin网络架构的影响.
主要方法:
- 在DCM患者队列中,使用化高性能液体染色学对DES基因的突变查.
- 已识别的DES突变转移到细胞模型中 (SW13,光滑肌细胞,新生小鼠心肌细胞).
- 使用共聚焦显微镜分析desmin蛋白位址和细胞骨网络形成.
主要成果:
- 在425名DCM受试者中有6名 (1.4%的患病率) 发现了5种新的误解DES突变.
- 在DES 2B域中的突变导致了细胞质内desmin蛋白的显著破坏和凝聚.
- 一个尾部域突变 (Val459Ile) 对desmin网络表现出较轻微的影响,并且似乎是低透性突变,主要在黑人个体中.
结论:
- 在DCM病例中,DES突变占1-2%,其中1A和2B域的突变具有病原性.
- 致病性desmin突变可以导致DCM,即使看似完好无损的desmin网络结构,特别是那些在1A和尾部域.
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