TBK1 mutation frequencies in French frontotemporal dementia and amyotrophic lateral sclerosis cohorts

Isabelle Le Ber, Anne De Septenville, Stéphanie Millecamps, Agnès Camuzat, Paola Caroppo, Philippe Couratier, Frédéric Blanc, Lucette Lacomblez, François Sellal, Marie Céline Fleury, Vincent Meininger, Cécile Cazeneuve, Fabienne Clot, Olivier Flabeau, Eric LeGuern, Alexis Brice

Research output: Contribution to journalArticlepeer-review


TANK1-binding kinase 1 (TBK1) has been recently identified as a new amyotrophic lateral sclerosis (ALS) gene. Loss-of-function (LoF) mutations in TBK1 could be responsible for 0.4%-4% of ALS. Considering the strong genetic overlap existing between frontotemporal dementia (FTD) and ALS, we have evaluated the frequencies of TBK1 mutations in a cohort of French FTD and of ALS patients. We identified 5 LoF mutations, in 4 FTD-ALS and 1 ALS patients. We also identified 5 heterozygous missense variants, predicted to be deleterious, in 1 isolated FTD, 1 FTD-ALS, and 3 ALS cases. Our results demonstrate that TBK1 loss-of-function mutations are more frequent in patients with FTD-ALS (10.8%) than in isolated ALS. TBK1 should thus also be sequenced, after exclusion of C9orf72 mutation, in patients presenting FTD, particularly in cases secondarily associated with ALS.

Original languageEnglish
JournalNeurobiology of Aging
Issue number11
Publication statusPublished - Nov 1 2015


  • Amyotrophic lateral sclerosis (ALS)
  • Frontotemporal dementia (FTD)
  • Frontotemporal lobar degeneration (FTLD)
  • Loss of function
  • Optineurin
  • TBK1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology


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