关注多聚谷氨酰胺病的修饰基因研究

Focus on genetic modifiers of polyglutamine diseases

多聚谷氨酰胺病是一组具有高度临床和遗传异质性的神经退行性疾病,由致病基因外显子中CAG三核苷酸重复发生动态突变引起,表现为神经系统特定区域选择性的神经元死亡。总体而言,CAG重复序列拷贝数可解释多聚谷氨酰胺病发病年龄50%~70%的变异,修饰基因也对其临床异质性有影响。文中回顾了多聚谷氨酰胺病的修饰基因研究历程,简述了主要发现和对研究现状的思考。

Polyglutamine(PolyQ)diseases are a group of clinically and genetically heterogeneous neurodegenerative diseases,due to an expanded CAG repeat in a coding region of the respective genes leading to neurodegenerative phenotypes by selective neuronal loss.Overall,only part of variance(50%-70%)in age at onset is explained by(CAG)n length,suggesting genetic modifying factors independent of(CAG)n size may contribute to clinical heterogeneity.Here,the research history of genetic modifiers in polyQ diseases is reviewed,and the major findings and current research status are discussed.