Abstract
Spinocerebellar ataxia type 3 (SCA3) is caused by unstable expanded CAG repeats (expCAGs) in ATXN3. Factors associated with intergenerational instability (delta-expCAG) and genetic anticipation in SCA3 have never been reported in Chinese mainland. Here, we demonstrated that unstable transmissions occurred more often in sons than in daughters (91% vs 72%, Fisher’s exact test, p = 0.012). The extended delta-expCAG of father-son transmissions was greater than that of mother-son transmissions (3.8 ± 2.3 repeats vs 1.6 ± 1.0 repeats, Mann-Whitney U, p = 0.001). Genetic anticipation was frequently observed between generations but not affected by the delta-expCAG.
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Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Acknowledgments
We would like to thank all participants for their willingness to join this study.
Funding
This work was supported by the research foundation for distinguished scholar of Zhejiang University to Zhi-Ying Wu (188020-193810101/089, Hangzhou).
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Yi-Chu Du: data collection, analysis and interpretation, and draft of the manuscript.
Yin Ma: administrative and technical support and data analysis and interpretation.
Ya-Ru Shao: data collection.
Shi-Rui Gan: data collection.
Yi Dong: data collection and analysis and interpretation.
Zhi-Ying Wu: study concept and design, data acquiring, analysis and interpretation, and critical revision of the manuscript.
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This study was performed in line with the principles of the Declaration of Helsinki. And the study was approved by the ethics committees of the Second Affiliated Hospital of Zhejiang University (Hangzhou), the First Affiliated Hospital of Fujian Medical University (Fuzhou), and Huashan Hospital of Fudan University (Shanghai).
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Du, YC., Ma, Y., Shao, YR. et al. Factors Associated with Intergenerational Instability of ATXN3 CAG Repeat and Genetic Anticipation in Chinese Patients with Spinocerebellar Ataxia Type 3. Cerebellum 19, 902–906 (2020). https://doi.org/10.1007/s12311-020-01167-x
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DOI: https://doi.org/10.1007/s12311-020-01167-x