Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, The Netherlands; International Max Planck Research School for Language Sciences, Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, The Netherlands.
Language and Genetics Department, Max Planck Institute for Psycholinguistics, 6525 XD Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 EN Nijmegen, The Netherlands.
Curr Opin Genet Dev. 2020 Dec;65:103-111. doi: 10.1016/j.gde.2020.05.012. Epub 2020 Jul 1.
Rare genetic variants that disrupt speech development provide entry points for deciphering the neurobiological foundations of key human capacities. The value of this approach is illustrated by FOXP2, a transcription factor gene that was implicated in speech apraxia, and subsequently investigated using human cell-based systems and animal models. Advances in next-generation sequencing, coupled to de novo paradigms, facilitated discovery of etiological variants in additional genes in speech disorder cohorts. As for other neurodevelopmental syndromes, gene-driven studies show blurring of boundaries between diagnostic categories, with some risk genes shared across speech disorders, intellectual disability and autism. Convergent evidence hints at involvement of regulatory genes co-expressed in early human brain development, suggesting that etiological pathways could be amenable for investigation in emerging neural models such as cerebral organoids.
罕见的遗传变异会破坏语言发育，为揭示人类关键能力的神经生物学基础提供了切入点。这种方法的价值体现在 FOXP2 基因上，该基因是一种转录因子基因，与言语运动障碍有关，随后使用基于人类细胞的系统和动物模型进行了研究。下一代测序技术的进步，加上从头开始的范例，促进了在言语障碍队列中发现其他基因的病因变体。对于其他神经发育综合征，基因驱动的研究表明，诊断类别之间的界限变得模糊，一些风险基因在言语障碍、智力障碍和自闭症中共享。趋同的证据表明，早期人类大脑发育中共同表达的调节基因可能参与其中，这表明病因途径可能适合在新兴的神经模型中进行研究，如大脑类器官。
