Genetic and phenotypic spectrum of amyotrophic lateral sclerosis patients with CCNF variants from a large Chinese cohort

Abstract

Abstract Background: Cyclin F (CCNF) variants have been found to be associated with amyotrophic lateral sclerosis (ALS) / frontotemporal dementia (FTD). However, the genetic and clinical characteristics of ALS patients carrying CCNFvariants are largely unknown. Methods: Genetic analysis was performed in 1587 Chinese ALS patients and the missense variants were predicted by software. Additionally, we searched PubMed, Embase and Web of Science for relevant literatures and conducted a meta-analysis of the frequency of variants. Results: In our ALS cohort, we identified 29 nonsynonymous variants in 41 ALS patients, among which, 18 ALS patients (1.1%) carried 15 rare missense variants which were considered as probably pathogenic variants and 11 of 15 variants were novel. Seven relevant studies were identified and a total of 43 CCNFvariants in 59 ALS patients with a frequency of 0.8% were reported. The ratio of male to female in our cohort (10/8) was similar to that in Caucasians (4/7) and significantly higher than that in Asians (10/1). The proportion of bulbar onset in Caucasian CCNF carriers was similar to our cohort (25.0% vs. 27.8%), however, bulbar onset had never been reported in previous Asian studies (0/11). FTD was not found in CCNF carriers in previous Asian studies and our cohort, but it has been reported in a FALS cohorts (1/75) in Caucasians. Conclusion: There were some differences in the clinical characteristics among different ethnic ALS populations. More basic scientific researches are needed to elucidate the pathogenic mechanisms and genotype-phenotype associations of CCNF variants.