), 宋伟1, 徐婧2() 1. 东北师范大学心理学院, 长春 130024
2. 长春中医药大学临床医学院, 长春130117
收稿日期:2018-05-19出版日期:2018-12-15发布日期:2018-10-30通讯作者:巨兴达,徐婧E-mail:juxd513@nenu.edu.cn;xuj391@nenu.edu.cn基金资助:*全国教育科学“十二五”规划教育部青年专项课题“儿童孤独症的基因靶向教育策略研究”资助(EBA140364)CHRM3 gene and autism spectrum disorder
JU Xingda1(), SONG Wei1, XU Jing2() 1. School of Psychology, Northeast Normal University, Changchun 130024, China
2. School of Clinical Medicine, Changchun University of Chinese Medicine, Changchun 130117, China
Received:2018-05-19Online:2018-12-15Published:2018-10-30Contact:JU Xingda,XU Jing E-mail:juxd513@nenu.edu.cn;xuj391@nenu.edu.cn摘要/Abstract
摘要： 孤独症谱系障碍是一类具有遗传基础的儿童发展障碍疾病。近些年, 研究者们从分子病理学层面发现中枢胆碱能神经系统异常与孤独症患者认知和行为异常存在相关性。尸检研究、临床案例、动物模型研究均发现毒蕈碱型(M型)乙酰胆碱受体异常和孤独症的发生有着密切的关系。在以小鼠为模型的行为学研究中, 编码毒蕈碱型乙酰胆碱受体Ⅲ亚型的CHRM3基因突变会导致小鼠出现认知障碍、刻板行为等孤独症样表现。深入了解CHRM3基因的功能将能够帮助研究者进一步解释孤独症的相关行为特征, 为孤独症儿童教育方案的制定提供新的思路和方法。
图/表 4
表1孤独症家系研究中的CHRM3突变
| 突变类型 | 等位基因改变 | 氨基酸改变 | 遗传模式 | 参考文献 |
|---|---|---|---|---|
| 无义突变 | c.1762C>T | p.Gln588Ter | 家系遗传 | Li et al., (2017) |
| 错义突变 | c.1504A>G | p.Ile502Val | 新生突变 | De Rubeis et al., (2014) |
| 错义突变 | c.1423A>T | p.Ile475Phe | 新生突变 | |
| 缺失 | — | — | 新生突变 | Perrone et al., (2012) |
| 缺失 | — | — | 未知 | Petersen AK et al., (2012) |
表1孤独症家系研究中的CHRM3突变
| 突变类型 | 等位基因改变 | 氨基酸改变 | 遗传模式 | 参考文献 |
|---|---|---|---|---|
| 无义突变 | c.1762C>T | p.Gln588Ter | 家系遗传 | Li et al., (2017) |
| 错义突变 | c.1504A>G | p.Ile502Val | 新生突变 | De Rubeis et al., (2014) |
| 错义突变 | c.1423A>T | p.Ile475Phe | 新生突变 | |
| 缺失 | — | — | 新生突变 | Perrone et al., (2012) |
| 缺失 | — | — | 未知 | Petersen AK et al., (2012) |
图1CHRM3信号传导模式图。CHRM3可能通过“Gq-PLC-第二信使”信号通路调控神经细胞的增殖、运动、分化、突起生长和兴奋性
图1CHRM3信号传导模式图。CHRM3可能通过“Gq-PLC-第二信使”信号通路调控神经细胞的增殖、运动、分化、突起生长和兴奋性表2两名CHRM3基因缺失的孤独症患者的临床表现对比
| 特征 | Perrone等人报道的患者 | Andrea Klunder Petersen等人报道的患者 |
|---|---|---|
| 年龄、性别 | 7岁, 男 | 3岁7个月, 男 |
| 智力缺陷 | + | + |
| 发育迟缓 | + | + |
| 孤独症行为 | + | + |
| 癫痫 | - | - |
| 进食困难 | + | + |
| 身材短小 | + | - |
| 体重偏轻 | + | - |
| 曲指 | + | - |
| 斜视 | + | + |
| 自伤倾向 | + | + |
| 脑部核磁共振造影 | 正常 | 正常 |
| 社交退缩 | + | + |
| 言语发育迟缓 | + | + |
| 运动发育迟缓 | + | NA |
表2两名CHRM3基因缺失的孤独症患者的临床表现对比
| 特征 | Perrone等人报道的患者 | Andrea Klunder Petersen等人报道的患者 |
|---|---|---|
| 年龄、性别 | 7岁, 男 | 3岁7个月, 男 |
| 智力缺陷 | + | + |
| 发育迟缓 | + | + |
| 孤独症行为 | + | + |
| 癫痫 | - | - |
| 进食困难 | + | + |
| 身材短小 | + | - |
| 体重偏轻 | + | - |
| 曲指 | + | - |
| 斜视 | + | + |
| 自伤倾向 | + | + |
| 脑部核磁共振造影 | 正常 | 正常 |
| 社交退缩 | + | + |
| 言语发育迟缓 | + | + |
| 运动发育迟缓 | + | NA |
图2CHRM3异常在脑与个体不同水平上的影响
图2CHRM3异常在脑与个体不同水平上的影响参考文献 103
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