在TOP3A中具有新型同卵性变异的儿科患者的心脏移植结果,导致线粒体功能障碍
J Ganesh1, C Donnelly1, A Ligezka2
1Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America.
Molecular genetics and metabolism
|October 11, 2025
概括
TOP3A基因中的致病变体会导致多系统性疾病. 这一案例突出显示了一名患有TOP3A变体相关的线粒体功能障碍和心脏问题,但没有布鲁姆综合征特征的儿科患者.
科学领域:
- 遗传学和分子生物学
- 心脏病学 心脏病学
- 神经学 神经学
背景情况:
- TOP3A基因中的致病变体与多系统性疾病有关.
- 之前的研究发现了成年人患有线粒体功能障碍的病例和儿科病例患有类似布卢姆综合征的特征.
研究的目的:
- 报告一名患有TOP3A基因变异的儿科病人的新病例.
- 描述临床表现,重点关注心脏和神经表现.
- 调查潜在的分子机制,特别是线粒体功能障碍.
主要方法:
- 整体外基因组测序以识别遗传变异.
- 临床评估包括神经学检查和心脏评估.
- 生物化学和组织学分析以评估线粒体功能.
主要成果:
- 一名11岁的男性呈现了新型TOP3A变异的同卵性.
- 临床特征包括肌肉病,动脉衰,心房导电缺陷和扩张性心肌病.
- 患者经历了急性不补偿性心力衰竭,需要机械支持.
- 实验室发现证实了线粒体功能障碍,支持TOP3A变种的致病性.
- 值得注意的是,这个病人没有布鲁姆综合征的特征.
结论:
- 这种情况扩大了TOP3A相关疾病的表型谱.
- TOP3A变种可以导致儿童严重的心脏并发症和线粒体功能障碍.
- 这位患者没有布鲁姆综合征特征,这表明TOP3A相关疾病中的遗传或分子异质性.
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