对于需要心脏移植的末期心肌病的遗传贡献
Yuri Kim1,2, Oddný Brattberg Gunnarsdóttir2, Anissa Viveiros3,4
1Division of Cardiovascular Medicine, Brigham and Women's Hospital (Y.K., B.M., C.E.S.).
Circulation. Genomic and precision medicine
|September 28, 2023
概括
基因测序确定了近一半的末期心肌病患者的病因,揭示了心脏移植接受者的基因变异患病率高于门诊病例. 这有助于诊断心力衰竭和指导家庭风险评估.
科学领域:
- 心脏病学 心脏病学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 晚期心力衰竭往往需要心脏移植.
- 异常心肌病是一种常见的诊断,当可治疗的原因被排除在外时.
- 未知的遗传原因可能是末期心肌病的基础.
研究的目的:
- 调查DNA序列分析,以确定末期非缺血性心肌病的未知原因.
- 为了比较最终阶段遗传原因的患病率与门诊心肌病病例的患病率.
主要方法:
- 整体外基因组和基因组测序在122个成人和儿科患者的心脏中进行.
- 分析包括核和线粒体基因组中的致病性/可能致病性变体.
- 评估了非人类微生物序列,并在心肌病队列中比较了变异频率.
主要成果:
- 在44.3%的样本中发现了致病性/可能致病性心肌病变体.
- 因果遗传变异的患病率在末期心肌病症中明显高于门诊病例.
- 在28个样本中检测到帕尔沃病毒基因组序列,其中两个样本显示出明显更高的水平.
结论:
- 致病变体和病毒性心肌炎在45.9%的患有无法解释的末期心肌病的患者中被发现.
- 在移植接受者中,有害的基因变异比在门诊患者中更频繁.
- 基因分析可以确定末期心肌病的原因,为患者和家人提供指导管理和风险分层.
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