Kleefstra Tjitske, Schenck Annette, Kramer Jamie M, van Bokhoven Hans
Radboud University Medical Center, Department of Human Genetics, Nijmegen Center for Molecular Life Sciences (NCMLS), Nijmegen, The Netherlands.
Radboud University Medical Center, Department of Human Genetics, Nijmegen Center for Molecular Life Sciences (NCMLS), Nijmegen, The Netherlands; Radboud University Medical Center, Department of Cognitive Neurosciences, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Neuropharmacology. 2014 May;80:83-94. doi: 10.1016/j.neuropharm.2013.12.025. Epub 2014 Jan 13.
Cognitive disorders (CDs) are a heterogeneous group of disorders for which the genetic foundations are rapidly being uncovered. The large number of CD-associated gene mutations presents an opportunity to identify common mechanisms of disease as well as molecular processes that are of key importance to human cognition. Given the disproportionately high number of epigenetic genes associated with CD, epigenetic regulation of gene transcription is emerging as a process of major importance in cognition. The cognate protein products of these genes often co-operate in shared protein complexes or pathways, which is reflected in similarities between the neurodevelopmental phenotypes corresponding to these mutant genes. Here we provide an overview of the genes associated with CDs, and highlight some of the epigenetic regulatory complexes involving multiple CD genes. Such common gene networks may provide a handle for designing therapeutic interventions applicable to a number of cognitive disorders with variable genetic etiology.
认知障碍(CDs)是一组异质性疾病,其遗传基础正迅速被揭示。大量与CD相关的基因突变提供了一个机会,可用于识别疾病的共同机制以及对人类认知至关重要的分子过程。鉴于与CD相关的表观遗传基因数量异常之多,基因转录的表观遗传调控正成为认知中一个至关重要的过程。这些基因的同源蛋白产物通常在共享的蛋白复合物或途径中协同作用,这反映在与这些突变基因相对应的神经发育表型之间的相似性上。在此,我们概述了与CDs相关的基因,并强调了一些涉及多个CD基因的表观遗传调控复合物。此类共同的基因网络可能为设计适用于多种具有不同遗传病因的认知障碍的治疗干预措施提供线索。