双性病原性PARS2变异会导致发育性和性脑病变,在睡眠中发生尖峰和波激活
Laura Licchetta1, Lucia Di Giorgi1,2, Margherita Santucci3
1IRCCS Istituto delle Scienze Neurologiche di Bologna, Full member of the European Reference Network EpiCARE Bologna, Bologna, Italy.
Molecular genetics & genomic medicine
|December 13, 2023
概括
这项研究确定了PARS2基因中的致病变体,导致发育性和性脑病变,在睡眠中具有尖端和波动激活 (DEE-SWAS). 它强调PARS2是DEE-SWAS的新型遗传原因,扩大了诊断可能性.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 儿科 儿科 儿科
背景情况:
- 线粒体prolyl-tRNA合成酶2基因 (PARS2) 中的双性致病变体与发育性和性脑病变-75 (DEE-75) 有关.
- DEE-75通常表现为早期发作,智力障碍,小头症,并且往往预后不佳,大多数患者在10岁以后无法生存.
- 关键特征包括耐火性婴儿,高心律失常,大脑缩,低髓化,乳酸性酸和心肌病.
研究的目的:
- 为了研究早期发作的性脑病变的遗传基础,具有特定的EEG模式.
- 为了确定综合性性脑病变的新型遗传原因.
- 探索与PARS2基因变异相关的电临床表型.
主要方法:
- 在患有早期DEE的患者身上进行了详细的临床,代谢和遗传研究.
- 整体外基因组测序 (WES) 用于识别致病性遗传变异.
- 一个全面的文献综述专注于PARS2-关联DEE的电临床特征.
主要成果:
- 在该患者身上发现了PARS2基因中的复合异构合致病变体.
- 该患者表现出一致的睡眠时尖峰和波激活 (SWAS) EEG模式,这是PARS2相关的DEE中以前没有报道的特征.
- 与典型病例不同,这位患者在没有心脏问题或乳酸性酸症的情况下表现出更长的生存期,这表明了潜在的基因修饰者.
结论:
- 这些发现扩大了DEE-SWAS的遗传谱,确定PARS2是这种疾病的致病基因.
- 这项研究强调了长时间睡眠EEG监测对诊断SWAS的重要性,可能是PARS2相关的DEE不断演变的电临床表现.
- 临床表现的变异性表明基因修饰剂在PARS2相关的神经发育障碍中的影响.
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