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Identification of the Largest SCA36 Pedigree in Asia: with Multimodel Neuroimaging Evaluation for the First Time

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Abstract

Spinocerebellar ataxias (SCAs) are a large group of hereditary neurodegenerative diseases characterized by ataxia and dysarthria. Due to high clinical and genetic heterogeneity, many SCA families are undiagnosed. Herein, using linkage analysis, WES, and RP-PCR, we identified the largest SCA36 pedigree in Asia. This pedigree showed some distinct clinical characteristics. Cognitive impairment and gaze palsy are common and severe in SCA36 patients, especially long-course patients. Although no patients complained of hearing loss, most of them presented with hearing impairment in objective auxiliary examination. Voxel-based morphometry (VBM) demonstrated a reduction of volumes in cerebellum, brainstem, and thalamus (corrected P < 0.05). Reduced volumes in cerebellum were also found in presymptomatic carriers. Resting-state functional MRI (R-fMRI) found reduced ReHo values in left cerebellar posterior lobule (corrected P < 0.05). Diffusion tensor imaging (DTI) demonstrated a reduction of FA values in cerebellum, midbrain, superior and inferior cerebellar peduncle (corrected P < 0.05). MRS found reduced NAA/Cr values in cerebellar vermis and hemisphere (corrected P < 0.05). Our findings could provide new insights into management of SCA36 patients. Detailed auxiliary examination are recommended to assess hearing or peripheral nerve impairment, and we should pay more attention to eye movement and cognitive changes in patients. Furthermore, for the first time, our multimodel neuroimaging evaluation generate a full perspective of brain function and structure in SCA36 patients.

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Data Availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We thank all of the participants for their involvement in this study.

Funding

This study was funded by the National Key Research and Development Program of China (No. 2016YFC0905100 and No. 2016YFC0901504 to H Jiang; No. 2016YFC1306000 to B Tang), the National Natural Science Foundation of China (No. 81771231 and No. 81974176 to H Jiang; No. 81901169 to Z Chen; No. 81901305 to C Wang; No. 81600995 to Y Shi), the Innovation Research Group Project of Natural Science Foundation of Hunan Province (No. 2020JJ1008 to H Jiang), the Science and Technology Innovation Group of Hunan Province (No. 2020RC4043 to H Jiang), the Scientific Research Foundation of Health Commission of Hunan Province (No. B2019183 to H Jiang), the Key Research and Development Program of Hunan Province (No. 2020SK2064 and No. 2018SK2092 to H Jiang), the Innovative Research and Development Program of Development and Reform Commission of Hunan Province to H Jiang, the Natural Science Foundation of Hunan Province (No. 2019JJ40363 to R Qiu), the Clinical and Rehabilitation Funds of Peking University Weiming Biotech Group (No. xywm2015I10 to H Jiang), the Project Program of National Clinical Research Center for Geriatric Disorders (Xiangya Hospital, No. 2020LNJJ12 and No. XYYYJSTG-05 to H Jiang), and the Youth Foundation of Xiangya Hospital (No. 2017Q03 to Z Chen, No. 2018Q05 to C Wang).

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Yue Xie, Zhao Chen, Ming-Jie Liu, Lin-Liu Peng, Hui-Rong Peng, Na Wan, Guangdong Zou, Yu-Ting Shi, Bei-Sha Tang & Hong Jiang

  2. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China

    Zhao Chen, Bei-Sha Tang & Hong Jiang

  3. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhao Chen, Bei-Sha Tang & Hong Jiang

  4. School of Basic Medicine, Central South University, Changsha, Hunan, China

    Hong Jiang

  5. Department of Neurology, Xiangya Second Hospital, Central South University, Changsha, Hunan, China

    Zhe Long

  6. Department of Radiology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Rui-Ting Chen, Gao-Feng Zhou & Wei-Hua Liao

  7. Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China

    Yi-Zheng Jiang, Zheng-Mao Hu & Kun Xia

  8. Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, Hunan, China

    Yi-Zheng Jiang, Zheng-Mao Hu & Kun Xia

  9. Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Chun-Rong Wang

  10. School of Computer Science and Engineering, Central South University, Changsha, Hunan, China

    Rong Qiu

  11. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, China

    Zhao Chen & Hong Jiang

Authors
  1. Yue Xie
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  2. Zhao Chen
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  3. Zhe Long
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  6. Ming-Jie Liu
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  7. Lin-Liu Peng
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  9. Na Wan
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  13. Gao-Feng Zhou
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  15. Rong Qiu
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  16. Zheng-Mao Hu
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  17. Kun Xia
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  18. Bei-Sha Tang
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  19. Hong Jiang
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Contributions

Yue Xie: conception and design of the study, acquisition and analysis of data, writing. Zhao Chen, Zhe Long, Rui-Ting Chen, Yi-Zheng Jiang, Lin-Liu Peng, Ming-Jie Liu, Hui-Rong Peng, Na Wan, Guangdong Zou: acquisition and analysis of data. Chun-Rong Wang, Zhao Chen, Yu-Ting Shi, Gao-Feng Zhou, Wei-Hua Liao, Rong Qiu, Zheng-Mao Hu, Kun Xia, Bei-Sha Tang: funding acquisition, writing—review and editing, supervision. Hong Jiang: conception and design of the study, funding acquisition, writing—review and editing, supervision.

Corresponding author

Correspondence to Hong Jiang.

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This study was approved by the Ethics Committee of Xiangya Hospital, Central South University, and written informed consent were obtained from all of the participants.

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The authors declare no competing interests.

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Xie, Y., Chen, Z., Long, Z. et al. Identification of the Largest SCA36 Pedigree in Asia: with Multimodel Neuroimaging Evaluation for the First Time. Cerebellum 21, 358–367 (2022). https://doi.org/10.1007/s12311-021-01304-0

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