Department of Human Genetics, Ingham Institute, School of Medicine, University of Western Sydney, Sydney, NSW, Australia.
Transl Psychiatry. 2012 Sep 4;2(9):e158. doi: 10.1038/tp.2012.75.
Tourette syndrome (TS) is a highly heritable neuropsychiatric disorder characterised by motor and vocal tics. Despite decades of research, the aetiology of TS has remained elusive. Recent successes in gene discovery backed by rapidly advancing genomic technologies have given us new insights into the genetic basis of the disorder, but the growing collection of rare and disparate findings have added confusion and complexity to the attempts to translate these findings into neurobiological mechanisms resulting in symptom genesis. In this review, we explore a previously unrecognised genetic link between TS and a competing series of trans-synaptic complexes (neurexins (NRXNs), neuroligins (NLGNs), leucine-rich repeat transmembrane proteins (LRRTMs), leucine rich repeat neuronals (LRRNs) and cerebellin precursor 2 (CBLN2)) that links it with autism spectrum disorder through neurodevelopmental pathways. The emergent neuropathogenetic model integrates all five genes so far found to be uniquely disrupted in TS into a single pathogenetic chain of events described in context with clinical and research implications.
妥瑞氏症（TS）是一种高度遗传性的神经精神疾病，其特征为运动和发声抽动。尽管研究了数十年，但 TS 的病因仍然难以捉摸。基因发现的最新成功，加上快速发展的基因组技术，使我们对该疾病的遗传基础有了新的认识，但越来越多的罕见和不同的发现增加了将这些发现转化为导致症状产生的神经生物学机制的复杂性。在这篇综述中，我们探讨了 TS 与一系列竞争的突触间复合物（神经连接蛋白（NRXNs）、神经连接素（NLGNs）、富含亮氨酸重复跨膜蛋白（LRRTMs）、富含亮氨酸重复神经元（LRRNs）和小脑前体 2（CBLN2））之间以前未被识别的遗传联系，通过神经发育途径将其与自闭症谱系障碍联系起来。新兴的神经发病机制模型将迄今为止在 TS 中唯一发现被破坏的所有五个基因整合到一个单一的发病链事件中，该模型结合了临床和研究意义进行了描述。
