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.

扰乱言语发展的罕见遗传变异为解密关键人类能力的神经生物学基础提供了切入点。该方法的价值由FOXP2阐明，FOXP2是一种与言语失用症有关的转录因子基因，随后使用基于人细胞的系统和动物模型进行了研究。新一代测序技术的进步，以及从头开始范例，促进了语言障碍队列中其他基因的病因变异发现。至于其他神经发育综合症，基因驱动的研究显示诊断类别之间的界限模糊了，一些危险基因在言语障碍，智力障碍和自闭症中共享。越来越多的证据表明，共表达的调控基因参与了人类早期大脑的发育，这表明病原学途径可能适合于在新兴的神经模型（如脑器官）中进行研究。