The progression rate of spinocerebellar ataxia type 3 varies with disease stage

Author:

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 HongORCID

Abstract

Abstract Background In polyglutamine (polyQ) diseases, the identification of modifiers and the construction of prediction model for progression facilitate genetic counseling, clinical management and therapeutic interventions. Methods 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. Results 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. Conclusions 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.

Funder

the National Key R&D Program of China

National Key Research and Development Program of China

National Natural Science Foundation of China

Innovation Research Group Project of Natural Science Foundation of Hunan Province

Science and Technology Innovation Group of Hunan Province

Scientific Research Foundation of Health Commission of Hunan Province

Key Research and Development Program of Hunan Province

Innovative Research and Development Program of Development and Reform Commission of Hunan Province

Natural Science Foundation of Hunan Province

Project Program of National Clinical Research Center for Geriatric Disorders

Publisher

Springer Science and Business Media LLC

Subject

General Biochemistry, Genetics and Molecular Biology,General Medicine

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