Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio, United States of America.
PLoS One. 2012;7(9):e44736. doi: 10.1371/journal.pone.0044736. Epub 2012 Sep 12.
Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic.
METHODOLOGY/PRINCIPAL FINDINGS: To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling.
CONCLUSIONS/SIGNIFICANCE: This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
自闭症是一种常见的神经发育综合征。有许多罕见的遗传病因被报道；大多数病例是特发性的。
方法/主要发现：为了揭示自闭症中的重要基因失调，我们使用高分辨率全基因组基因表达和全基因组 DNA 甲基化微阵列分析了精心挑选的特发性自闭症和对照小脑和 BA19（枕叶）脑组织。在自闭症大脑中未发现 DNA 甲基化的变化，但代谢的两个区域的基因表达异常明显：线粒体氧化磷酸化和蛋白质翻译的基因下调。我们还发现自闭症的特定行为领域与与髓鞘/髓鞘形成、炎症/免疫反应和嘌呤能信号传导相关的特定脑基因表达模块之间存在关联。
结论/意义：这项工作强调了自闭症中两个尚未被广泛认识的分子病理生理学主题，并提示了自闭症行为表型的不同分子基础。
