Investigating CCNF mutations in a Taiwanese cohort with amyotrophic lateral sclerosis

Neurobiol Aging. 2018 Feb:62:243.e1-243.e6. doi: 10.1016/j.neurobiolaging.2017.09.031. Epub 2017 Oct 9.


Mutations in the cyclin F gene (CCNF) have been recently identified in a small number of patients with amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia, and their role in patients with ALS in Taiwan remains elusive. The aim of this study was to elucidate the frequency and spectrum of CCNF mutations in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of the CCNF gene were performed using Sanger sequencing in a cohort of 255 unrelated patients with ALS. Among these patients, the genetic diagnoses of 204 patients remained unclear after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, HNRNPA2B1, MATR3, CHCHD10, TUBA4A, and TKB1 had been investigated. Two novel heterozygous missense mutations in CCNF, p.S222P (c.664T>C) and p.S532R (c.1596C>T), were identified; 1 in each patient with apparently sporadic ALS. In vitro functional study demonstrated that both mutations result in a general and cyclin F-mediated ubiquitin-proteasome pathway dysfunction. The frequency of CCNF mutations in ALS patients in Taiwan is, therefore, approximately 0.8% (2/255). These findings expand the mutational spectrum of CCNF and also emphasize the pathogenic role of CCNF mutations in ALS.

Keywords: ALS; Amyotrophic lateral sclerosis; CCNF; Cyclin F.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / genetics*
  • Asian People / genetics
  • Cohort Studies
  • Cyclins / genetics*
  • Female
  • Genetic Association Studies*
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Mutation*
  • Proteasome Endopeptidase Complex
  • Proteolysis
  • Taiwan
  • Ubiquitination
  • Young Adult


  • CCNF protein, human
  • Cyclins
  • Proteasome Endopeptidase Complex