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

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.