The progression rate of spinocerebellar ataxia type 3 varies with disease stage.
The progression rate of spinocerebellar ataxia type 3 varies with disease stage.
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3 型脊髓小脑共济失调的进展率随疾病阶段而变化
DOI：
10.1186/s12967-022-03428-1
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发表时间：
2022-05-14
影响因子：
7.4
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
--
作者：
Peng, Linliu;Peng, Yun;Chen, Zhao;Wang, Chunrong;Long, Zhe;Peng, Huirong;Shi, Yuting;Shen, Lu;Xia, Kun;Leotti, Vanessa B.;Jardim, Laura Bannach;Tang, Beisha;Qiu, Rong;Jiang, Hong
在多聚谷氨酰胺（polyQ）疾病中，鉴定修饰物和构建进展预测模型有助于遗传咨询、临床管理和治疗干预。数据来源于最长的纵向研究，采用国际合作共济失调评定量表（ICARS）对82名SCA 3参与者进行了642次检查。使用不同的疾病持续时间的时间尺度，我们进行了多个不同的线性，二次和分段线性增长模型，以拟合ICARS评分和持续时间之间的关系。采用模型比较法，根据拟合优度检验和嵌套模型间方差分析确定最佳拟合模型。在13年的持续时间后检测到加速：ICARS评分在此截止日期前每年进步2.445（SE：0.185）分，在此截止日期后每年进步3.547（SE：0.312）分。分段生长模型比其他两类模型更适合研究数据。ATXN 3基因中CAG重复序列长度（expanded CAG repeat，CAGexp）对疾病进展有显著影响。步态共济失调（AOga）的发病年龄，老化过程的代理，是不是一个独立的修改器，但影响CAGexp和进展之间的相关性。此外，性别对ICARS的进展率没有显著影响。确定分段增长模型作为预测模型，并利用相关模型进行ICARS预测。我们首次证实了ICARS的进展是一个非线性模式，并根据SCA 3的不同阶段而变化。除了ATXN 3 CAGexp外，AOga或衰老过程通过与CAGexp相互作用来调节进展。在线版本包含补充材料，可通过10.1186/s12967-022-03428-1获得。
In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions. Data were derived from the longest longitudinal study, with 642 examinations by International Cooperative Ataxia Rating Scale (ICARS) from 82 SCA3 participants. Using different time scales of disease duration, we performed multiple different linear, quadratic and piece-wise linear growth models to fit the relationship between ICARS scores and duration. Models comparison was employed to determine the best-fitting model according to goodness-of-fit tests, and the analysis of variance among nested models. An acceleration was detected after 13 years of duration: ICARS scores progressed 2.445 (SE: 0.185) points/year before and 3.547 (SE: 0.312) points/year after this deadline. Piece-wise growth model fitted better to studied data than other two types of models. The length of expanded CAG repeat (CAGexp) in ATXN3 gene significantly influenced progression. Age at onset of gait ataxia (AOga), a proxy for aging process, was not an independent modifier but affected the correlation between CAGexp and progression. Additionally, gender had no significant effect on progression rate of ICARS. The piece-wise growth models were determined as the predictive models, and ICARS predictions from related models were available. We first confirmed that ICARS progressed as a nonlinear pattern and varied according to different stages in SCA3. In addition to ATXN3 CAGexp, AOga or aging process regulated the progression by interacting with CAGexp. The online version contains supplementary material available at 10.1186/s12967-022-03428-1.
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影响因子：
10.6
作者：
Johnson EB;Ziegler G;Penny W;Rees G;Tabrizi SJ;Scahill RI;Gregory S
通讯作者：
Gregory S
影响因子：
3.2
作者：
Cansado-Utrilla, Cintia;Jeffries, Claire L.;Walker, Thomas
通讯作者：
Walker, Thomas
影响因子：
9.9
作者：
Jacobi, H.;Bauer, P.;Klockgether, T.
通讯作者：
Klockgether, T.
影响因子：
48
作者：
Jacobi, Heike;du Montcel, Sophie Tezenas;Klockgether, Thomas
通讯作者：
Klockgether, Thomas
影响因子：
48
作者：
Jacobi, Heike;du Montcel, Sophie Tezenas;Klockgether, Thomas
通讯作者：
Klockgether, Thomas