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Spinocerebellar Ataxia Type 10 with Atypical Clinical Manifestation in Han Chinese

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Abstract

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant cerebellar ataxia accompanied by extracerebellar signs and other neurological disorders. It is caused by an expansion of the ATTCT pentanucleotide repeat in intron 9 of ATXN10. Cases of SCA10, formerly confined to America, have been reported in Europe and Asia. In the present study, we aim to report an atypical SCA10 family in China and provide a reference for the diagnosis of SCA10 in Asia by comparing their clinical and genetic features with former SCA10 pedigrees. Genomic DNA was extracted from patients and subjected to RP-PCR (repeat-primed PCR), Southern blotting, and haplotype analysis to determine the genetic pathogenesis. Patients with SCA10 in this pedigree demonstrated atypical SCA10 manifestations, including the absence of seizures and ocular abnormalities. Magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients with available data. RP-PCR and Southern blotting revealed abnormal expansion. Analysis of single nucleotide polymorphisms (SNPs) surrounding the SCA10 locus in the proband and other affected family members revealed the “C-expansion-G-G-C” haplotype, consistent with former studies. These findings imply that the SCA10 mutation may have occurred before the Amerindian migration from East Asia to North America. It also suggested that SCA10 should be taken into account during differential diagnosis in patients of Asian ancestry, even if they do not present with typical features such as epilepsy.

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Funding

This study was funded by the National Natural Science Foundation of China (Grant U1904207, 91849115 and 81530037 to Dr. Yuming Xu, Grant 81771290 and 81974211 to Dr. Changhe Shi, Grant 81901300 to Dr. Chengyuan Mao), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant 2020-PT310-01 to Dr. Yuming Xu), the National Key Research and Development Program of China (Grant 2017YFA0105003 to Dr. Yuming Xu), and the Scientific and Technological Project of Henan Province (Grant SBGJ202003020 to Dr. Chengyuan Mao).

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Author notes

  1. Chengyuan Mao, Xinwei Li and Yun Su contributed equally to this article

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China

    Chengyuan Mao, Xinwei Li, Yun Su, Haiyang Luo, Liyuan Fan, Huimin Zheng, Yu Fan, Zhihua Yang, Shuo Zhang, Zhengwei Hu, Xiaoyan Hao, Changhe Shi & Yuming Xu

  2. Henan Key Laboratory of Cerebrovascular Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, China

    Chengyuan Mao, Xinwei Li, Yun Su, Haiyang Luo, Liyuan Fan, Huimin Zheng, Yu Fan, Zhihua Yang, Shuo Zhang, Zhengwei Hu, Xiaoyan Hao, Changhe Shi & Yuming Xu

  3. Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China

    Chengyuan Mao

  4. NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Diseases, Zhengzhou, Henan, China

    Chengyuan Mao, Changhe Shi & Yuming Xu

  5. Academy of Medical Sciences of Zhengzhou University, Zhengzhou, China

    Xinwei Li, Liyuan Fan, Yu Fan, Shuo Zhang, Zhengwei Hu & Xiaoyan Hao

  6. Institute of Neuroscience, Zhengzhou University, Zhengzhou, China

    Changhe Shi & Yuming Xu

Authors
  1. Chengyuan Mao
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  2. Xinwei Li
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  3. Yun Su
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  10. Zhengwei Hu
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  11. Xiaoyan Hao
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  12. Changhe Shi
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  13. Yuming Xu
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Chengyuan Mao, Xinwei Li, and Yun Su. The first draft of the manuscript was written by Chengyuan Mao and Xinwei Li. Analysis or interpretation of data was performed by Yun Su, Haiyang Luo, Liyuan Fan, Huimin Zheng, Yu Fan, Zhihua Yang, Shuo Zhang, Zhengwei Hu, and Xiaoyan Hao. This study was supervised by Yuming Xu and Changhe Shi. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Changhe Shi or Yuming Xu.

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Ethics Approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.

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Informed consent was obtained from all individual participants included in this study.

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Mao, C., Li, X., Su, Y. et al. Spinocerebellar Ataxia Type 10 with Atypical Clinical Manifestation in Han Chinese. Cerebellum 22, 355–362 (2023). https://doi.org/10.1007/s12311-022-01405-4

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