Frontiers in Cellular Neuroscience ( IF 4.2 ) Pub Date : 2020-12-15 , DOI: 10.3389/fncel.2020.611379 Josan Gandawijaya , Rosemary A. Bamford , J. Peter H. Burbach , Asami Oguro-Ando
Autism spectrum disorder (ASD) is characterized by impaired social interaction, language delay and repetitive or restrictive behaviors. With increasing prevalence, ASD is currently estimated to affect 0.5–2.0% of the global population. However, its etiology remains unclear due to high genetic and phenotypic heterogeneity. Copy number variations (CNVs) are implicated in several forms of syndromic ASD and have been demonstrated to contribute toward ASD development by altering gene dosage and expression. Increasing evidence points toward the p-arm of chromosome 3 (chromosome 3p) as an ASD risk locus. Deletions occurring at chromosome 3p result in 3p-deletion syndrome (Del3p), a rare genetic disorder characterized by developmental delay, intellectual disability, facial dysmorphisms and often, ASD or ASD-associated behaviors. Therefore, we hypothesize that overlapping molecular mechanisms underlie the pathogenesis of Del3p and ASD. To investigate which genes encoded in chromosome 3p could contribute toward Del3p and ASD, we performed a comprehensive literature review and collated reports investigating the phenotypes of individuals with chromosome 3p CNVs. We observe that high frequencies of CNVs occur in the 3p26.3 region, the terminal cytoband of chromosome 3p. This suggests that CNVs disrupting genes encoded within the 3p26.3 region are likely to contribute toward the neurodevelopmental phenotypes observed in individuals affected by Del3p. The 3p26.3 region contains three consecutive genes encoding closely related neuronal immunoglobulin cell adhesion molecules (IgCAMs):
中文翻译:
细胞粘附分子参与3p缺失综合征和自闭症谱系牵连的神经发育途径。
自闭症谱系障碍(ASD)的特征是社交互动受损,语言延迟以及重复或限制性行为。随着患病率的提高,目前估计ASD会影响全球人口的0.5–2.0%。然而,由于高度的遗传和表型异质性,其病因仍不清楚。拷贝数变异(CNV)涉及多种形式的ASD综合征,并已证明可通过改变基因剂量和表达来促进ASD的发展。越来越多的证据表明,第3号染色体的p臂(3p染色体)是ASD的危险源。3p染色体缺失会导致3p缺失综合症(Del3p),这是一种罕见的遗传疾病,其特征在于发育延迟,智力残疾,面部畸形以及经常与ASD或ASD相关的行为。因此,我们假设重叠的分子机制是Del3p和ASD发病机制的基础。为了研究3p染色体中编码的哪些基因可能对Del3p和ASD起作用,我们进行了全面的文献综述并整理了有关研究3p染色体CNV个体表型的报告。我们观察到高频率的CNV发生在3p26.3区域,即3p染色体的末端细胞带。这表明CNVs破坏编码在3p26.3区域内的基因可能有助于在受Del3p影响的个体中观察到的神经发育表型。3p26.3区包含三个连续的基因,这些基因编码紧密相关的神经元免疫球蛋白细胞粘附分子(IgCAM):为了研究3p染色体中编码的哪些基因可能对Del3p和ASD起作用,我们进行了全面的文献综述并整理了有关研究3p染色体CNV个体表型的报告。我们观察到高频率的CNV发生在3p26.3区域,即3p染色体的末端细胞带。这表明CNVs破坏编码在3p26.3区域内的基因可能有助于在受Del3p影响的个体中观察到的神经发育表型。3p26.3区包含三个连续的基因,这些基因编码紧密相关的神经元免疫球蛋白细胞粘附分子(IgCAM):为了研究3p染色体中编码的哪些基因可能对Del3p和ASD起作用,我们进行了全面的文献综述并整理了有关研究3p染色体CNV个体表型的报告。我们观察到高频率的CNV发生在3p26.3区域,即3p染色体的末端细胞带。这表明CNVs破坏编码在3p26.3区域内的基因可能有助于在受Del3p影响的个体中观察到的神经发育表型。3p26.3区包含三个连续的基因,这些基因编码紧密相关的神经元免疫球蛋白细胞粘附分子(IgCAM):我们观察到高频率的CNV发生在3p26.3区域,即3p染色体的末端细胞带。这表明CNVs破坏编码在3p26.3区域内的基因可能有助于在受Del3p影响的个体中观察到的神经发育表型。3p26.3区包含三个连续的基因,这些基因编码紧密相关的神经元免疫球蛋白细胞粘附分子(IgCAM):我们观察到CNV的高频出现在3p26.3区域,即3p染色体的末端细胞带。这表明CNVs破坏编码在3p26.3区域内的基因可能有助于在受Del3p影响的个体中观察到的神经发育表型。3p26.3区包含三个连续的基因,这些基因编码紧密相关的神经元免疫球蛋白细胞粘附分子(IgCAM):