Diaw Sokhna Haissatou, Ott Fabian, Münchau Alexander, Lohmann Katja, Busch Hauke
Institute of Neurogenetics, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany.
Institute of Experimental Dermatology and Institute of Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany.
Med Genet. 2022 Aug 12;34(2):131-141. doi: 10.1515/medgen-2022-2126. eCollection 2022 Jun.
Pathogenic variants in can cause dystonia with a penetrance of about 50 %. The underlying mechanisms are unknown and can be considered as means of endogenous disease protection. Since encodes a transcription factor, drivers of this variability putatively act at the transcriptome level. Several transcriptome studies tried to elucidate THAP1 function in diverse cellular and mouse models, including mutation carrier-derived cells and iPSC-derived neurons, unveiling various differentially expressed genes and affected pathways. These include nervous system development, dopamine signalling, myelination, or cell-cell adhesion. A network diffusion analysis revealed mRNA splicing, mitochondria, DNA repair, and metabolism as significant pathways that may represent potential targets for therapeutic interventions.
[基因名称]中的致病变异可导致肌张力障碍，其外显率约为50%。潜在机制尚不清楚，可被视为内源性疾病保护的方式。由于[基因名称]编码一种转录因子，这种变异性的驱动因素可能在转录组水平上起作用。多项转录组研究试图在不同的细胞和小鼠模型中阐明THAP1的功能，包括突变携带者来源的细胞和诱导多能干细胞衍生的神经元，揭示了各种差异表达的基因和受影响的通路。这些包括神经系统发育、多巴胺信号传导、髓鞘形成或细胞间粘附。网络扩散分析表明，mRNA剪接、线粒体、DNA修复和代谢是重要通路，可能代表治疗干预的潜在靶点。
