心肌病遗传学的年龄和性别差异
Oyediran Akinrinade1,2, Robert Lesurf1,
1Genetics and Genome Biology Program, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Journal of cardiovascular translational research
|July 21, 2023
概括
儿科心肌病患者携带的有害基因变异比成年人更多,特别是在sarcomere基因中. 这些遗传差异影响疾病的表现和透率,影响疾病发病年龄,并指导遗传咨询.
科学领域:
- 遗传学 遗传学 是一个
- 心脏病学 心脏病学
- 基因组医学是基因组医学.
背景情况:
- 心肌病表现出可变的透率,这表明潜在的遗传因素影响疾病表现.
- 了解与年龄和性别相关的遗传变异对于诊断和管理心肌病至关重要.
研究的目的:
- 研究心肌病患者的年龄和性别特异性遗传差异.
- 为了确定与儿科与成人发作的心肌病相关的特定基因变异.
- 探索扩张性心肌病中与性别相关的差异的遗传基础.
主要方法:
- 全基因组测序对来自安大略省和英国的1397名心肌病患者进行.
- 分析了基因变异,比较儿科 (n=471) 和成人 (n=926) 队列.
- 评估了特定基因类别 (肉瘤,通道病变,z盘) 的变异负担和丰富性.
主要成果:
- 儿科心肌病患者在Tier 1基因中具有有害蛋白质编码变异的负担较高 (34.6%对25.9%,p=0.0015).
- 儿科病例显示,与成人相比,萨尔科默尔基因变异增加 (例如,MYH7,MYL3) 和通道病变基因变异减少.
- 成年人具有较高的OBSCN和TTN变异负担,而扩张性心肌病的女性比男性具有更多的z盘基因变异.
结论:
- 显著的年龄和性别相关的遗传差异存在于心肌病.
- 儿科和成人心肌病之间的遗传特征不同,具有不同的基因负担.
- 基因型导向的预测可以为有关心肌病发病和透性的遗传咨询提供信息.
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