The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration
The chromosome 6p22 haplotype associated with dyslexia reduces the expression of KIAA0319, a novel gene involved in neuronal migration
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DOI：
10.1093/hmg/ddl089
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发表时间：
2006-05-15
影响因子：
3.5
通讯作者：
Monaco, AP
中科院分区：
文献类型：
--
作者：
Paracchini, S;Thomas, A;Monaco, AP
阅读障碍是最常见的儿童认知障碍之一，影响约5%的学龄儿童。我们最近在染色体6p22.2上发现了一个与阅读障碍相关的风险单倍型，该单倍型跨越TTRAP基因以及THEM2和KIAA0319的部分。在这里，我们表明，在风险单倍型的存在下，KIAA0319基因的表达减少，但其他两个基因的表达保持不受影响。使用原位杂交，我们检测到一个非常独特的表达模式的KIAA0319基因在发育中的小鼠和人类胎儿的大脑新皮质。此外，在子宫内干扰大鼠Kiaa0319表达导致发育中的大脑新皮质中的神经元迁移受损。这些数据表明，特定的遗传背景和导致阅读障碍发展的生物学机制之间存在直接联系：染色体6p22.2上的风险单倍型下调了大脑新皮层形成期间神经元迁移所需的KIAA0319基因。
Dyslexia is one of the most prevalent childhood cognitive disorders, affecting similar to 5% of school-age children. We have recently identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 gene is reduced but the expression of the other two genes remains unaffected. Using in situ hybridization, we detect a very distinct expression pattern of the KIAA0319 gene in the developing cerebral neocortex of mouse and human fetuses. Moreover, interference with rat Kiaa0319 expression in utero leads to impaired neuronal migration in the developing cerebral neocortex. These data suggest a direct link between a specific genetic background and a biological mechanism leading to the development of dyslexia: the risk haplotype on chromosome 6p22.2 down-regulates the KIAA0319 gene which is required for neuronal migration during the formation of the cerebral neocortex.