Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study
Abstract Background Spinocerebellar ataxia type 3 (SCA3) is a hereditary disease caused by abnormally expanded CAG repeats in the ATXN3 gene. The study aimed to identify potential biomarkers for assessing therapeutic efficacy by investigating the associations between expanded CAG repeat size, brain...
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BMC
2025-01-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-025-03531-8 |
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| author | Zhi-Xian Ye Xuan-Yu Chen Meng-Cheng Li Xin-Yuan Chen Yu-Sen Qiu Ru-Ying Yuan Zhi-Li Chen Min-Ting Lin Jian-Ping Hu Ying Fu Wan-Jin Chen Ning Wang Shi-Rui Gan on behalf of the OSCCAR Investigators |
| author_facet | Zhi-Xian Ye Xuan-Yu Chen Meng-Cheng Li Xin-Yuan Chen Yu-Sen Qiu Ru-Ying Yuan Zhi-Li Chen Min-Ting Lin Jian-Ping Hu Ying Fu Wan-Jin Chen Ning Wang Shi-Rui Gan on behalf of the OSCCAR Investigators |
| author_sort | Zhi-Xian Ye |
| collection | DOAJ |
| description | Abstract Background Spinocerebellar ataxia type 3 (SCA3) is a hereditary disease caused by abnormally expanded CAG repeats in the ATXN3 gene. The study aimed to identify potential biomarkers for assessing therapeutic efficacy by investigating the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in patients with SCA3. Methods In this prospective, cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between expanded CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) scores were investigated using partial correlation and mediation analyses. Sample sizes of potential biomarkers were calculated. Results Compared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. Expanded CAG repeat size was associated with right cerebellar lobule IV volume (r = − 0.423, P < 0.001) and cervical spinal cord area (r = − 0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of expanded CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cord measures. Conclusions Our results indicate the potential of cervical spinal cord area as a biomarker for disease progression and a minimum sample size estimation in future clinical studies of SCA3. |
| format | Article |
| id | doaj-art-01ab1b9aa18d49b8bab213e0e10c0c8f |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-01ab1b9aa18d49b8bab213e0e10c0c8f2025-01-26T12:52:16ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-0120111110.1186/s13023-025-03531-8Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort studyZhi-Xian Ye0Xuan-Yu Chen1Meng-Cheng Li2Xin-Yuan Chen3Yu-Sen Qiu4Ru-Ying Yuan5Zhi-Li Chen6Min-Ting Lin7Jian-Ping Hu8Ying Fu9Wan-Jin Chen10Ning Wang11Shi-Rui Gan12on behalf of the OSCCAR InvestigatorsDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversitySchool of Basic Medical Sciences, Fujian Medical UniversityDepartment of Radiology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Rehabilitation Medicine of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Radiology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurology of First Affiliated Hospital, Fujian Medical UniversityAbstract Background Spinocerebellar ataxia type 3 (SCA3) is a hereditary disease caused by abnormally expanded CAG repeats in the ATXN3 gene. The study aimed to identify potential biomarkers for assessing therapeutic efficacy by investigating the associations between expanded CAG repeat size, brain and spinal cord volume loss, and motor functions in patients with SCA3. Methods In this prospective, cross-observational study, we analyzed 3D T1-weighted MRIs from 92 patients with SCA3 and 42 healthy controls using voxel-based morphometry and region of interest approaches. Associations between expanded CAG repeat size, brain and spinal cord volume loss, and International Cooperative Ataxia Rating Scale (ICARS) scores were investigated using partial correlation and mediation analyses. Sample sizes of potential biomarkers were calculated. Results Compared with healthy controls, SCA3 patients had lower cerebellar volume and cervical spinal cord area. SCA3 patients evolved along a stage-independent decline that began in the cerebellum, progressed to spinal cord, brainstem, thalami, and basal ganglia, and extensive subcortex. Expanded CAG repeat size was associated with right cerebellar lobule IV volume (r = − 0.423, P < 0.001) and cervical spinal cord area (r = − 0.405, P < 0.001), and higher ICARS (r = 0.416, P < 0.001). Mediation analysis revealed an indirect effect of expanded CAG repeat size on ICARS through spinal cord. Sample sizes estimation revealed that a minimum sample size was achieved with spinal cord measures. Conclusions Our results indicate the potential of cervical spinal cord area as a biomarker for disease progression and a minimum sample size estimation in future clinical studies of SCA3.https://doi.org/10.1186/s13023-025-03531-8CAG repeat sizeSpinal cordSample sizeMRISCA3 |
| spellingShingle | Zhi-Xian Ye Xuan-Yu Chen Meng-Cheng Li Xin-Yuan Chen Yu-Sen Qiu Ru-Ying Yuan Zhi-Li Chen Min-Ting Lin Jian-Ping Hu Ying Fu Wan-Jin Chen Ning Wang Shi-Rui Gan on behalf of the OSCCAR Investigators Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study Orphanet Journal of Rare Diseases CAG repeat size Spinal cord Sample size MRI SCA3 |
| title | Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study |
| title_full | Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study |
| title_fullStr | Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study |
| title_full_unstemmed | Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study |
| title_short | Associations between CAG repeat size, brain and spinal cord volume loss, and motor symptoms in spinocerebellar ataxia type 3: a cohort study |
| title_sort | associations between cag repeat size brain and spinal cord volume loss and motor symptoms in spinocerebellar ataxia type 3 a cohort study |
| topic | CAG repeat size Spinal cord Sample size MRI SCA3 |
| url | https://doi.org/10.1186/s13023-025-03531-8 |
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