Department of Human Genetics, Department of Cognitive Neuroscience, Radboudumc, 6500 HB, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
Department of Human Genetics, Department of Cognitive Neuroscience, Radboudumc, 6500 HB, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition, and Behaviour, Centre for Neuroscience, 6525 AJ, Nijmegen, The Netherlands.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jun 8;84(Pt B):382-391. doi: 10.1016/j.pnpbp.2017.11.009. Epub 2017 Nov 8.
A major challenge in clinical genetics and medicine is represented by genetically and phenotypically highly diverse neurodevelopmental disorders, like for example intellectual disability and autism. Intellectual disability is characterized by substantial limitations in cognitive function and adaptive behaviour. At the cellular level, this is reflected by deficits in synaptic structure and plasticity and therefore has been coined as a synaptic disorder or "synaptopathy". In this review, we summarize the findings from recent studies in which iPSCs have been used to model specific neurodevelopmental syndromes, including Fragile X syndrome, Rett syndrome, Williams-Beuren syndrome and Phelan-McDermid syndrome. We discuss what we have learned from these studies and what key issues need to be addressed to move the field forward.
临床遗传学和医学面临的一个主要挑战是具有高度遗传和表型多样性的神经发育障碍，例如智力障碍和自闭症。智力障碍的特征是认知功能和适应行为有实质性的限制。在细胞水平上，这反映在突触结构和可塑性的缺陷上，因此被称为突触障碍或“突触病”。在这篇综述中，我们总结了最近使用 iPSC 来模拟特定神经发育综合征的研究结果，包括脆性 X 综合征、雷特综合征、威廉姆斯综合征和苯丙酮尿症-麦克德米德综合征。我们讨论了从这些研究中学到了什么，以及为了推动该领域的发展需要解决哪些关键问题。
