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.