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Autosomal Recessive Cerebellar Ataxia Type 1: Phenotypic and Genetic Correlation in a Cohort of Chinese Patients with SYNE1 Variants

The Cerebellum volume 20, pages 74–82 (2021)Cite this article

Abstract

Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene have been reported to cause autosomal recessive cerebellar ataxia (ARCA) type 1 with highly variable clinical phenotypes. The aim of this study was to describe the phenotypic-genetic spectrum of SYNE1-related ARCA1 patients in the Chinese population. We screened 158 unrelated patients with autosomal recessive or sporadic ataxia for variants in SYNE1 using next-generation sequencing. Pathogenicity assessment of SYNE1 variants was interpreted according to the American College of Medical Genetics standards and guidelines. We identified eight truncating variants and two missense variants spreading throughout the SYNE1 gene from six unrelated families, including nine novel variants and one reported variant. Of the six index patients, two patients showed the classical pure cerebellar ataxia, while four patients exhibited non-cerebellar phenotypes, including motor neuron symptoms, cognitive impairment, or mental retardation. The variants associated with motor neuron or cognition involvement tend to be located in the C-terminal region of SYNE1 protein, compared with the variants related to pure cerebellar ataxia. Our data indicating SYNE1 mutation is one of the more common causes of recessive ataxia in the Chinese population. The use of next-generation sequencing has enabled the rapid analysis of recessive ataxia and further expanded our understanding of genotype-phenotype correlation.

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Acknowledgments

We are grateful to all the patients and family members for their generous participation in this study.

Author information

Affiliations

  1. Movement Disorder and Neurogenetics Research Center, Department of Neurology, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China

    Xiaohui Duan, Ying Hao, Jin Zhang, Renbin Wang, Shaojie Sun & Weihong Gu

  2. Running Gene Inc, Beijing, 100191, China

    Zhenhua Cao & Chao Zhou

Authors
  1. Xiaohui Duan
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  2. Ying Hao
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  3. Zhenhua Cao
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  4. Chao Zhou
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  5. Jin Zhang
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  6. Renbin Wang
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  7. Shaojie Sun
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  8. Weihong Gu
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Contributions

Conceived and designed the project: W.H.G. and X.H.D. Performed the experiments: X.H.D., Y.H., C.Z., and X.Z. Analyzed the data: X.H.D., Y.H., and J.Z. Contributed to the writing of the manuscript: All authors have made a significant contribution and have approved the final version of this manuscript.

Corresponding author

Correspondence to Weihong Gu.

Ethics declarations

This study was approved by the Ethics Committee of China-Japan Friendship Hospital. The methods in this study were performed in accordance with the approved guidelines. Written informed consent was obtained from all the patients.

Conflict of Interest

The authors declare that they have no conflict of interest.

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This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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Duan, X., Hao, Y., Cao, Z. et al. Autosomal Recessive Cerebellar Ataxia Type 1: Phenotypic and Genetic Correlation in a Cohort of Chinese Patients with SYNE1 Variants. Cerebellum 20, 74–82 (2021). https://doi.org/10.1007/s12311-020-01186-8

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  • DOI: https://doi.org/10.1007/s12311-020-01186-8

Keywords

  • Autosomal recessive cerebellar ataxia 1(ARCA1)
  • SYNE1 gene
  • Genotype
  • Phenotype
  • Whole-exome sequencing (WES)