School of Biology, College of Science, University of Tehran, Tehran, Iran; Genetic Research Center, University of social welfare and Rehabilitation Sciences, Tehran, Iran.
Genetic Research Center, University of social welfare and Rehabilitation Sciences, Tehran, Iran.
Neuroscience. 2019 Apr 15;404:423-444. doi: 10.1016/j.neuroscience.2019.01.029. Epub 2019 Feb 10.
A significant level of genetic heterogeneity has been demonstrated in intellectual disability (ID). More than 700 genes have been identified in ID patients. To identify molecular pathways underlying this heterogeneity, we applied whole-transcriptome analysis using RNA-Seq in consanguineous families with ID. Significant changes in expression of genes related to neuronal and actin cytoskeletal functions were observed in all the ID families. Remarkably, we found a significant down-regulation of SHTN1 gene and up-regulation of FGFR2 gene in all ID patients. FGFR2, but not SHTN1, was previously reported as an ID causing gene. Detailed gene ontology analyses identified pathways linked to tyrosine protein kinase, actin cytoskeleton, and axonogenesis to be affected in ID patients. The findings reported here provide new insights into the candidate genes and molecular pathways underling ID and highlight the key role of actin cytoskeleton in etiology of ID.
在智力障碍（ID）中已经证明存在显著的遗传异质性。已经在 ID 患者中鉴定出超过 700 个基因。为了确定这种异质性的分子途径，我们在 ID 患者的近亲家庭中应用了 RNA-Seq 进行全转录组分析。在所有 ID 家庭中都观察到与神经元和肌动蛋白细胞骨架功能相关的基因表达显著变化。值得注意的是，我们发现所有 ID 患者的 SHTN1 基因表达显著下调，FGFR2 基因表达上调。FGFR2 基因先前被报道为导致 ID 的基因，但 SHTN1 基因不是。详细的基因本体分析确定了与酪氨酸蛋白激酶、肌动蛋白细胞骨架和轴突发生相关的途径受到 ID 患者的影响。这里报道的发现为 ID 的候选基因和分子途径提供了新的见解，并强调了肌动蛋白细胞骨架在 ID 病因学中的关键作用。
