产期心肌病的遗传和表现特征
Rahul Goli1, Jian Li1, Jeff Brandimarto1
1Cardiovascular Institute, and Penn Muscle Institute, Department of Medicine (R.G., J.L., J. Brandimarto, Q.M., K.B.M., T.P.C., Z.A.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Circulation
|April 20, 2021
概括
遗传因素有助于产周心肌病 (PPCM). 这项研究在PPCM患者中确定了TTN,FLNC,DSP和BAG3基因变异,揭示了与扩张性心肌病的相似之处,并提供了遗传咨询.
科学领域:
- 心脏病学
- 遗传学
- 母亲健康
背景情况:
- 产前心肌病 (PPCM) 影响约2000分之一的分娩,但其遗传原因尚不清楚.
- 虽然约10%的PPCM病例中发现了TTN的截断变体 (TTNtvs),但其他基因的作用和TTNtv对临床表现和结果的影响尚不清楚.
- 在PPCM中,TTNtvs的患病率尚未确定,特别是与已知危险因素 - - 孕前有关.
研究的目的:
- 通过分析广泛的基因来研究产期心肌病 (PPCM) 的遗传基础.
- 确定PPCM女性中TTN (TTNtvs) 和其他基因中截断变异的流行率.
- 评估PPCM患者的遗传变异,临床表现和结果之间的关联.
主要方法:
- 在多个中心对469名PPCM妇女的临床数据和DNA样本进行了回顾性分析.
- 67个基因的下一代测序,包括TTN,以识别截断和错误变异.
- 对TTNtvs对临床表现严重程度和患者结果的影响的统计评估.
主要成果:
- 在10. 4%的PPCM患者中发现了TTNtvs,明显高于参考人群 (OR=9. 4, P*=1.2×10−46).
- 在FLNC (OR=24.8),DSP (OR=14.9) 和BAG3 (OR=53.1) 中的截断变异也在PPCM中过度表现,首次涉及这些基因.
- 患有TTNtvs的女性表现出左下心室喷射分数 (23. 5% vs. 29%,P=2. 5×10−4),但表现出表现时间,孕前患病率或康复率没有显著差异.
结论:
- 遗传倾向,特别是TTN,FLNC,DSP和BAG3的变异,在PPCM的发展中起着重要作用.
- PPCM与非缺血性扩张性心肌病具有遗传相似性,这表明共享治疗策略和遗传检测方法的潜力.
- 了解PPCM中的基因型-表型相关性对于准确的遗传咨询和个性化的患者管理至关重要.
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