University of California at Davis, M.I.N.D., Institute and Department of Neurology, USA.
Brain Res. 2011 Mar 24;1381:228-36. doi: 10.1016/j.brainres.2011.01.026. Epub 2011 Jan 15.
Tourette syndrome (TS) is a complex childhood neurodevelopmental disorder characterized by motor and vocal tics. Recently, altered numbers of GABAergic-parvalbumin (PV) and cholinergic interneurons were observed in the basal ganglia of individuals with TS. Thus, we postulated that gamma-amino butyric acid (GABA)- and acetylcholine (ACh)-related genes might be associated with the pathophysiology of TS. Total RNA isolated from whole blood of 26 un-medicated TS subjects and 23 healthy controls (HC) was processed on Affymetrix Human Exon 1.0 ST arrays. Data were analyzed to identify genes whose expression correlated with tic severity in TS, and to identify genes differentially spliced in TS compared to HC subjects. Many genes (3627) correlated with tic severity in TS (p < 0.05) among which GABA- (p = 2.1 × 10⁻³) and ACh- (p = 4.25 × 10⁻⁸) related genes were significantly over-represented. Moreover, several GABA and ACh-related genes were predicted to be alternatively spliced in TS compared to HC including GABA receptors GABRA4 and GABRG1, the nicotinic ACh receptor CHRNA4 and cholinergic differentiation factor (CDF). This pilot study suggests that at least some of these GABA- and ACh-related genes observed in blood that correlate with tics or are alternatively spliced are involved in the pathophysiology of TS and tics.
妥瑞氏综合征（TS）是一种复杂的儿童神经发育障碍，其特征是运动和发声抽动。最近，在妥瑞氏综合征患者的基底神经节中观察到 GABA 能性-副甲状腺球蛋白（PV）和胆碱能中间神经元的数量发生改变。因此，我们假设γ-氨基丁酸（GABA）和乙酰胆碱（ACh）相关基因可能与 TS 的病理生理学有关。从 26 名未经治疗的 TS 患者和 23 名健康对照者（HC）的全血中分离出总 RNA，在 Affymetrix Human Exon 1.0 ST 阵列上进行处理。对数据进行分析，以确定与 TS 抽搐严重程度相关的基因，并确定与 HC 受试者相比在 TS 中差异剪接的基因。许多基因（3627 个）与 TS 中的抽搐严重程度相关（p < 0.05），其中 GABA-（p = 2.1 × 10⁻³）和 ACh-（p = 4.25 × 10⁻⁸）相关基因明显过表达。此外，与 HC 相比，一些 GABA 和 ACh 相关基因被预测在 TS 中发生选择性剪接，包括 GABA 受体 GABRA4 和 GABRG1、烟碱型 ACh 受体 CHRNA4 和胆碱能分化因子（CDF）。这项初步研究表明，在血液中观察到的至少一些与抽搐相关或发生选择性剪接的 GABA 和 ACh 相关基因可能与 TS 的病理生理学和抽搐有关。
