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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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.
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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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DOI: https://doi.org/10.1007/s00415-022-11042-w