亨廷顿舞蹈症发病的时间不是由聚谷氨酰胺的长度决定，而是由基因决定，特别是CAG重复序列。这一成果由亨廷顿舞蹈症(GeM-HD)基因修饰物联合会取得。2019年8月9日出版的《细胞》杂志发表了这一成果。

不同的谷氨酸编码CAA中断表明，不间断的HTT CAG重复序列的特性决定了亨廷顿病(HD)的发展速度，这不同于亨廷顿病的聚谷氨酰胺片段的长度。发病时间与HTT顺式eQTL没有显着关联，但有时以性别特异性方式受到多个DNA维持基因的多态性变异的影响。这倾向于解释不间断CAG重复的特殊起始决定了特性，而长度不稳定导致了体细胞扩张。GWAS定义的其他天然存在的基因修饰位点可能通过其他机制影响HD发病机制。这些发现对HD和其他重复疾病的发病机制具有深远的意义，并质疑了聚谷氨酰胺长度决定“多聚谷氨酰胺疾病“发病率这一个论断。

亨廷顿舞蹈症是一种常染色体显性遗传性神经退行性疾病，患者一般在中年发病，出现运动、认知和精神方面的症状。

附：英文原文

Title: CAG Repeat Not Polyglutamine Length Determines Timing of Huntington’s Disease Onset

Author: Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium

Issue&Volume: Volume 178 Issue 4

Abstract: Variable, glutamine-encoding, CAA interruptions indicate that a property of the uninterrupted HTT CAG repeat sequence, distinct from the length of huntingtin’s polyglutamine segment, dictates the rate at which Huntington’s disease (HD) develops. The timing of onset shows no significant association with HTT cis-eQTLs but is influenced, sometimes in a sex-specific manner, by polymorphic variation at multiple DNA maintenance genes, suggesting that the special onset-determining property of the uninterrupted CAG repeat is a propensity for length instability that leads to its somatic expansion. Additional naturally occurring genetic modifier loci, defined by GWAS, may influence HD pathogenesis through other mechanisms. These findings have profound implications for the pathogenesis of HD and other repeat diseases and question the fundamental premise that polyglutamine length determines the rate of pathogenesis in the “polyglutamine disorders.”

DOI: https://doi.org/10.1016/j.cell.2019.06.036

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)30739-1