CHRM3基因与孤独症谱系障碍

doi:10.3724/SP.J.1042.2018.02141

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。

关键词: 孤独症谱系障碍, CHRM3基因, 临床特征, 动物模型

Abstract:

Autism Spectrum Disorder is one of the most complex developmental disorders with a strong genetic impact. In recent years, researchers have increasingly linked effects of central cholinergic system dysfunction to autism-related cognitive and behavioral abnormalities at the molecular pathological level. Results from autopsy studies, clinical cases and animal experiments revealed that aberrant muscarinic acetylcholine receptors have a strong relationship with autism. In behavioral studies using mouse models, the variations of CHRM3 gene, which encodes the muscarinic acetylcholine receptor subtype III receptor, can cause autistic phenotypes such as cognitive impairment and stereotypic behavior. Accordingly, in-depth functional understanding of CHRM3 gene may have important implications to further explain the characteristics and mechanisms of autistic behavior and may potentially provide new ideas and methods for the development of educational programs for autistic children.

Key words: autism spectrum disorder, CHRM3 gene, clinical features, animal models

中图分类号:

B845

巨兴达, 宋伟, 徐婧. (2018). CHRM3基因与孤独症谱系障碍. 心理科学进展 , 26(12), 2141-2152.

JU Xingda, SONG Wei, XU Jing. (2018). CHRM3 gene and autism spectrum disorder. Advances in Psychological Science, 26(12), 2141-2152.

图/表 4

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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	Li et al. (2017)
缺失	—	—	新生突变	Perrone et al., (2012)
缺失	—	—	未知	Petersen AK et al., (2012)

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	Li et al. (2017)
缺失	—	—	新生突变	Perrone et al., (2012)
缺失	—	—	未知	Petersen AK et al., (2012)

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

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

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