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Delineation of molecular basis of autism using array CGH

使用阵列 CGH 描述自闭症的分子基础

基本信息

批准号：
21591341
负责人：
KOSAKI Rika
金额：
$ 2.66万
依托单位：
National Research Institute for Child Health and Development
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2011
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591341/
关键词：
小児神経学オリゴDNAアレイ CGH法自閉症遺伝アレイCGH

项目摘要

Autism is a complex developmental disability that typically appears during the first three years of life and is the result of a neurological disorder that affects the normal functioning of the brain, impacting development in the areas of social interaction and communication skills. Presumably, genetic background contributes to autism. Yet, only 10% of patients exhibit definitive genetic abnormalities. We designed a custom array with 60000 probes. Probes were densely allocated at genes on X chromosome, genes of which mutations are known to cause multiple malformation syndromes with developmental delay(i. e. Cornelia de Lange syndrome, Rubinstein-Taybi syndrome), and genes already known to be related with autism(NLGN3, NGLN4, NRXN1, SHANK3, CNTNAP2, PCDH10, CNTN3, NHE9, NHE6, DIA1, and A2BP1) and their homologous/upstream/downstream genes.We have identified two critical cases : One patient who had a duplication of 5.4MB at 6q14, 2-15 including the GABA receptor GABRB3 ; the other patient had a deletion of 6.6MB at 2p16.3 including NRXN1. NRXN forms a complex with NLGN on the post synaptic membrane and plays a critical role on neural transmission mediated through GABA receptors and glutamine receptors. We suggest that duplication of GABRB3 and deletion of NRXN1 contributes to autism.

自闭症是一种复杂的发育障碍，通常出现在生命的前三年，是影响大脑正常功能的神经系统疾病的结果，影响社会互动和沟通技能领域的发展。据推测，遗传背景有助于自闭症。然而，只有10%的患者表现出明确的遗传异常。我们设计了一个带有60000个探针的定制阵列。探针密集地分布在X染色体上的基因上，这些基因的突变已知会导致具有发育迟缓的多种畸形综合征（即，e.科尔内利亚德兰格综合征，鲁宾斯坦-泰比综合征），以及已知与自闭症相关的基因（NLGN 3、NGLN 4、NRXN 1、SHANK 3、CNTNAP 2、PCDH 10、CNTN 3、NHE 9、NHE 6、DIA 1和A2 BP 1）及其同源/上游/下游基因的研究。另一位患者在2p16.3有6.6MB的缺失，包括NRXN 1。NRXN与NLGN在突触后膜上形成复合物，并在通过GABA受体和谷氨酰胺受体介导的神经传递中起关键作用。我们认为GABRB 3的重复和NRXN 1的缺失有助于自闭症。