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Genotype–phenotype association of TARDBP mutations in Chinese patients with amyotrophic lateral sclerosis: a single-center study and systematic review of published literature

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Abstract

Background

This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS) combined with data in the literature.

Methods

We performed TARDBP mutation screening in 1258 Chinese ALS patients, including 1204 sporadic ALS (sALS) and 54 familial ALS (fALS) patients. A systematic literature review was conducted by searching TARDBP-mutated patients from China in the online databases.

Results

In our cohort, the mutant frequency of TARDBP variants was 0.3% (4/1258), with two recurrent variants (p.G294V, p.G298V) and one novel variant (p.S332G) identified. Combining with data in the literature review, the TARDBP-mutant frequency in the Chinese population was 1.4% (83/5998), with 0.8% (46/5470) in sALS and 7.0% (37/528) in fALS. Most patients had limb onset (63.0%), with an average life expectancy of 4.3 years (range 0.5–13). Disease durations significantly differed (p = 0.002), with p.M337V showing the longest duration (80 months) and p.N378D showing the shortest duration (16.7 months).

Conclusion

Our study found that TARDBP mutation was not rare in Chinese fALS patients. Different TARDBP mutations were associated with specific features in phenotypes.

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Acknowledgements

We thank the support of patients and their families. We also thank Miss Chen Wang for her great assistance in sample collecting and management.

Funding

This work was financially supported by the Strategic Priority Research Program of the Chinese Academy of Sciences “Biological basis of aging and therapeutic strategies” (Grant number: XDB39040100), the CAMS Innovation Fund for Medical Sciences (CIFMS) grant (Grant Number: 2016-I2M-1-002, 2021-1-I2M-018, and 2021-1-I2M-034), the National Natural Science Foundation of China (Grant Number: 81971293, 81788101), the National Key Research and Development Program of China (Grant Number 2016 YFC0905100).

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Authors and Affiliations

  1. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College (CAMS, PUMC), Beijing, China

    Jinyue Li, Qing Liu, Xiaohan Sun, Kang Zhang, Shuangwu Liu, Zhili Wang, Xunzhe Yang, Mingsheng Liu & Liying Cui

  2. McKusick-Zhang Center for Genetic Medicine, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS, PUMC, Beijing, China

    Xue Zhang

  3. Neuroscience Center, CAMS, Beijing, China

    Qing Liu, Liying Cui & Xue Zhang

Authors
  1. Jinyue Li
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  2. Qing Liu
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  3. Xiaohan Sun
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  4. Kang Zhang
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  5. Shuangwu Liu
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  6. Zhili Wang
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  8. Mingsheng Liu
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  10. Xue Zhang
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Contributions

JL: conceptualization, methodology, software, writing—original draft preparation. QL: conceptualization, writing—reviewing and editing. XS: data curation, investigation. KZ: data curation, visualization. SL: data curation, software. ZW: data curation, software. XY: investigation, validation. MSL: supervision, validation. LC: conceptualization, writing—reviewing and editing. XZ: supervision, validation.

Corresponding authors

Correspondence to Qing Liu or Liying Cui.

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Li, J., Liu, Q., Sun, X. et al. Genotype–phenotype association of TARDBP mutations in Chinese patients with amyotrophic lateral sclerosis: a single-center study and systematic review of published literature. J Neurol 269, 4204–4212 (2022). https://doi.org/10.1007/s00415-022-11042-w

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