AUTHOR=Gu Xiaojing , Chen Yongping , Wei Qianqian , Hou Yanbing , Cao Bei , Zhang Lingyu , Ou Ruwei , Lin Junyu , Liu Kuncheng , Zhao Bi , Shang Huifang 

TITLE=Rare CYLD Variants in Chinese Patients With Amyotrophic Lateral Sclerosis

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.740052

DOI=10.3389/fgene.2021.740052

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> CYLD Lysine 63 Deubiquitinase gene (<italic>CYLD</italic>) 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 <italic>CYLD</italic> in a large cohort of Chinese ALS patients, (2) study the genotype–phenotype correlation, and (3) explore the role of <italic>CYLD</italic> in ALS <italic>via</italic> rare variants burden analysis.</p><p><bold>Methods:</bold> 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 <italic>CYLD</italic> with minor allele frequency &lt;0.1%.</p><p><bold>Results:</bold> In total, seven rare missense variants in <italic>CYLD</italic> 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 <italic>CYLD</italic> among patients with ALS.</p><p><bold>Conclusion:</bold> In conclusion, our study extended the genotype and phenotype of <italic>CYLD</italic> in ALS, but the pathogenicity of these variants needs to be further verified. Moreover, burden analysis argued against the role of <italic>CYLD</italic> in the pathogenesis of ALS. More studies from different ethnicities would be needed.</p>