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

• Published in: Neurobiology of aging Vol. 36; no. 11; pp. 3116.e5 - 3116.e8
• Main Authors: Le Ber, Isabelle, De Septenville, Anne, Millecamps, Stéphanie, Camuzat, Agnès, Caroppo, Paola, Couratier, Philippe, Blanc, Frédéric, Lacomblez, Lucette, Sellal, François, Fleury, Marie-Céline, Meininger, Vincent, Cazeneuve, Cécile, Clot, Fabienne, Flabeau, Olivier, LeGuern, Eric, Brice, Alexis
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-11-2015
• Subjects: Amyotrophic lateral sclerosis (ALS); Amyotrophic Lateral Sclerosis - genetics; Cohort Studies; France; Frontotemporal dementia (FTD); Frontotemporal Dementia - genetics; Frontotemporal lobar degeneration (FTLD); Genetic Association Studies; Humans; Internal Medicine; Loss of function; Mutation - genetics; Mutation Rate; Neurology; Optineurin; Protein-Serine-Threonine Kinases - genetics; TBK1; France; Loss of function; TBK1; Optineurin; Frontotemporal lobar degeneration (FTLD); Amyotrophic lateral sclerosis (ALS); Frontotemporal dementia (FTD)
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2015.08.009

Abstract 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.