Rare Variants in Chinese Patients With Amyotrophic Lateral Sclerosis.

CYLD Lysine 63 Deubiquitinase gene () was recently identified to be a novel causative gene for frontal temporal dementia (FTD)-amyotrophic lateral sclerosis (ALS). In the current study, we aimed to (1) systematically screen the mutations of in a large cohort of Chinese ALS patients, (2) study the genotype-phenotype correlation, and (3) explore the role of in ALS rare variants burden analysis. A total of 978 Chinese sporadic ALS (sALS) patients and 46 familial ALS (fALS) patients were sequenced with whole-exome sequencing and analyzed rare variants in with minor allele frequency <0.1%. In total, seven rare missense variants in have been identified in 7 (0.72%) patients among 978 sALS patients. Two (4.3%) rare missense variants were identified among the 46 fALS cases, in which one patient was diagnosed as having comorbidity of ALS and progressive supranuclear palsy (PSP). Moreover, the burden analysis indicated no enrichment of rare variants in among patients with ALS. In conclusion, our study extended the genotype and phenotype of in ALS, but the pathogenicity of these variants needs to be further verified. Moreover, burden analysis argued against the role of in the pathogenesis of ALS. More studies from different ethnicities would be needed.