Validation of the pathogenic role of rare DNAJC7 variants in Chinese patients with amyotrophic lateral sclerosis

DNAJC7 has recently been recognized as a novel amyotrophic lateral sclerosis (ALS) risk gene. To date, few studies have screened DNAJC7 mutations in Chinese population. Further studies are needed to clarify the clinical and genetic features of DNAJC7-related ALS. Sporadic ALS (sALS) patients and controls were enrolled in this study. Variants were detected by whole-exome sequencing and validated via Sanger sequencing. Gene-based burden analysis was conducted. Potentially damaging variants in DNAJC7 were identified in 3 sALS patients. The frequency of bulbar onset was significantly higher in DNAJC7-related ALS patients than in the whole group. However, burden analysis showed no enrichment of rare DNAJC7 variants in sALS patients. Reported variant N369T showed no significant difference in distribution among different groups. In conclusion, DNAJC7 variants may be associated with ALS but not play a main role in Chinese patients. DNAJC7-related ALS patients tended to have a bulbar onset. Our study supported the pathogenic role of DNAJC7 in ALS and expanded the phenotypic and genetic spectrum of DNAJC7-related ALS.