Consortium study of search for susceptibility genes of pervasive developmental disorder

寻找广泛性发育障碍易感基因的联合研究

• 批准号: 16390320
• 负责人: SASAKI Tsukasa
• 金额: $ 9.02万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390320/
• 关键词: Pervasive developmental disorder; autism; susceptibility gene; association study; DNA methylation; poly-histidine repeat; ADHD; mutation; アミノ酸リピート; 遺伝子; 複雑疾患; 多因子遺伝; 神経線維症腫; 染色体7番長腕; 染色体15番長腕

This consortium study aimed to detect susceptibility genes of pervasive developmental disorders (PDD) including autism. We are recruiting PDD patients and the families, and thus far collected more than 300 hundred DNA samples of autism and other PDD patients, with the families' DNA in 240 patients. We analyzed candidate genes on the long-arm regions of choromosomes 2, 7 and 15 using the sample. The most extensively investigated were the genes on the chromosome 7 region, including TAC1, NPTX2, RELN, LAMB1, LAMB4, NRCAM, S-SCAM, FOXP2, PTPRZ1, WNT2, NPTX2 and other. We observed a significant association of the NRCAM polymorphisms, but no association of other genes, with PDD. In addition, we searched for a mutation in exons of a neuroligin-related molecule in PDD subjects, but no mutation has been found thus far. We also studied the Histidine region of the HOXA1 gene and found a novel polymorphism in autism patients. While the polymorphism finally proved to be not associated with autism, it caused a disturbance of cellular function which may lead to abnormal neuronal differentiation. It may be interesting to study what kind of developmental disorder the polymorphism is associated with. Other studies we conducted were an examination of the FMR triplet-repeat polymorphism (not the abnormal expansion), which was not associate with autism as a result, and an investigation of the allele-specific expression of MECP2 gene in lymphoblast from subjects with Rett syndrome. Mutation was observed in the methylated CpG binding domain of the gene in a half of the subjects. The mutation allele was not expressed however in most of the lymphoblast with the mutation.

这项联合研究旨在检测包括自闭症在内的普及性发育障碍(PDD)的易感基因。我们正在招募PDD患者及其家属，到目前为止，我们收集了300多份自闭症和其他PDD患者的DNA样本，其中240名患者的家属DNA。我们利用样本分析了染色体2、7和15的长臂区域的候选基因。研究最广泛的是7号染色体上的基因，包括Tac1、NPTX2、RELN、Lamb1、LAMB4、NrCAM、S-SCAM、FOXP2、PTPRZ1、WNT2、NPTX2等。我们观察到NrCAM多态与PDD有显著关联，但其他基因与PDD没有关联。此外，我们在PDD受试者中搜索了神经连接蛋白相关分子外显子的突变，但到目前为止还没有发现突变。我们还研究了HOXA1基因的组氨酸区域，并在自闭症患者中发现了一种新的多态性。虽然该基因多态性最终被证明与自闭症无关，但它导致了细胞功能障碍，可能导致神经元分化异常。研究这种多态与哪种发育障碍有关可能是很有趣的。我们进行的其他研究包括检测FMR三联体重复序列多态(而不是异常扩增)，结果与自闭症无关，以及研究Rett综合征患者淋巴母细胞中MECP2基因的等位基因特异性表达。在一半的受试者中，观察到该基因的甲基化CpG结合域发生突变。然而，突变等位基因在大多数带有突变的淋巴母细胞中不表达。

项目成果

No association of FOXP2 and PTPRZ1 on 7q31 with autism from the Japanese population.

7q31 上的 FOXP2 和 PTPRZ1 与日本人群的自闭症没有关联。

• 发表时间: 2005
• 期刊: Neuroscience Research 53
• 作者: Marui T;Koishi S;Funatogawa I;Yamamoto K;Matsumoto H;Hashimoto O;Nanba E;Kato C;Ishijima M;Watanabe K;Kasai K;Kato N;Sasaki T^*.
• 通讯作者: Sasaki T^*.

広汎性発達障害の臨床疫学

广泛性发育障碍的临床流行病学

• 发表时间: 2005
• 期刊: 臨床精神医学 34
• 作者: Narui T;Sasaki T他;佐々木 司
• 通讯作者: 佐々木 司

大学・大学院および職場における広汎性発達障害.

大学、研究生院和工作场所普遍存在发育障碍。

• 发表时间: 2005
• 期刊: 精神科 7
• 作者: Marui T;Koishi S;Funatogawa I;Yamamoto K;Matsumoto H;Hashimoto O;Nanba E;Kato C;Ishijima M;Watanabe K;Kasai K;Kato N;Sasaki T^*;佐々木司
• 通讯作者: 佐々木司

An association between the neurofibromatosis-1 (NF1) locus and autism in the Javanese population.

爪哇人群中神经纤维瘤病 1 (NF1) 基因座与自闭症之间的关联。

• 发表时间: 2004
• 期刊: Amrican Journal of Medical Genetics Part-B 131B
• 作者: Marui T;Hashimoto O;Nanba E;Kato C;Tochigi M;Umekage T;Kohda K;Kato N;Sasaki T^*.
• 通讯作者: Sasaki T^*.

Genetic factors in Asperger syndrome

阿斯伯格综合症的遗传因素

• 发表时间: 2007
• 期刊: Nihon-Rinsho 65
• 作者: Marui T;Koishi S;Funatogawa I;Yamamoto K;Matsumoto H;Hashimoto O;Ishijima M;Nanba E;Nishida H;Sugiyama T;Kasai K;Watanabe E;Kano Y;Kato N;Sasaki T.;Sasaki T
• 通讯作者: Sasaki T