Science:一种涉及基因修饰的人类心脏病的寡基因遗传

2019-07-12 Gladiator MedSci原创

研究人员发现1病例在妊娠24周时胎儿死亡。初步尸检结果表明,死亡原因是肺发育不良所导致。然而,研究人员对组织学切片的检查显示,胎儿双心室不致密,这是基于双心室心肌壁的深凹、右心室扩张和广泛的纤维化造成的(图1B)。直系亲心脏活体成像暴露了以前未被发现的证据,4岁的兄弟妹LVNC及其父亲的轻微LVNC迹象。研究对象的祖父有心律失常,但类似于大家庭成员,未发现心脏的功能或结构异常(图1 c)。总的来说

研究人员发现1病例在妊娠24周时胎儿死亡。初步尸检结果表明,死亡原因是肺发育不良所导致。然而,研究人员对组织学切片的检查显示,胎儿双心室不致密,这是基于双心室心肌壁的深凹、右心室扩张和广泛的纤维化造成的(1B)。直系亲心脏活体成像暴露了以前未被发现的证据,4岁的兄弟妹LVNC及其父亲的轻微LVNC迹象。研究对象的祖父有心律失常,但类似于大家庭成员,未发现心脏的功能或结构异常(图1 c)。总的来说,这些发现表明LVNC从父亲垂直传播,明显增加了疾病的严重程度和后代发病年龄。在发现上述病理学的基础上,为进一步研究该家族LVNC的潜在遗传原因,研究人员对该指示个案的直系亲属进行了全外显子组测序。并且推断,由于所有三个后代的外显率,个体的新生事件不太可能是疾病的原因,从而提出一种遗传变异假说。最初关注的是遗传自父亲的私有和/或罕见的(小等位基因频率,MAF < 0.005)外显子非同义变异,并确定了30个目标单核苷酸变异(SNVs)(2A,左)。这些变异中有8种经预测是有害的,但只有2种在心脏组织转录本中富集。研究人员进一步确定了3个感兴趣的基因,即MKL2, MYH7NKX2-5,并提出了它们可能一起产生便易导致了LVNC

本研究工作表明,对snv相关表型的实验探索是一个有价值的努力方向,因为它可以帮助我们阐明复杂疾病的机制。

原始出处:

Casey A. GiffordOligogenic inheritance of a human heart disease involving a genetic modifier

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    2019-07-16 130****4638

    学习了,谢谢分享。

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    2019-07-14 jichang
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    2019-07-14 zhangyxzsh
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