TBK1 variants in Chinese patients with amyotrophic lateral sclerosis

Abstract

TBK1 has been reported as a risk gene of amyotrophic lateral sclerosis (ALS). We screened TBK1 variants in 69 familial ALS patients and 608 sporadic ALS patients from mainland China. All 20 coding exons and the exon-intron flanking regions of TBK1 were amplified and sequenced using Sanger sequencing. In total, we identified eight missense variants and one suspicious splice site mutation. The patient with K291R had a family history of ALS. Other variants were detected in sALS patients. Interestingly, 2 patients with variants in TBK1 carried another variant in other genes related to autophagy: G175S in TBK1 and P392L in SQSTM1; and D534H in TBK1 and E372D in SQSTM1. We concluded that TBK1 variants account for approximately 1.3% of Chinese ALS patients. Screening for this gene in ALS patients is necessary, especially in the group with variants in other genes related to the autophagy pathway.

Keywords: Amyotrophic lateral sclerosis; China; Genetics; TBK1.