Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Am J Med Genet B Neuropsychiatr Genet. 2011 Dec;156B(8):941-8. doi: 10.1002/ajmg.b.31241. Epub 2011 Oct 10.
Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs.
语言障碍是自闭症和相关自闭症谱系障碍（ASD）的一个特征。自闭症也具有高度遗传性，在其发病机制中涉及的最有前途的候选基因之一是接触蛋白相关蛋白样 2（CNTNAP2），该基因也与语言障碍有关。在当前的研究中，我们使用功能磁共振成像（fMRI）在健康个体中研究了与自闭症和语言障碍相关的 CNTNAP2 变体的功能影响（rs7794745 和 rs2710102；分别为假定的风险等位基因 T 和 C），这些个体在执行语言任务时（n=66）。在正常表现和缺乏行为异常的背景下，具有假定风险等位基因的健康个体与没有表现出明显激活增加的个体相比，右侧额下回（Broca 区同源物）和右侧外侧颞叶皮层的激活增加。这些发现表明，CNTNAP2 基因中与风险相关的变异会影响健康非自闭症个体在语言处理任务中的大脑激活，为 CNTNAP2 基因遗传变异对 ASD 的核心特征的影响提供了证据。
