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

2015; Elsevier BV; Volume: 36; Issue: 11 Linguagem: Inglês

10.1016/j.neurobiolaging.2015.08.009

1558-1497

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, Sophie Auriacombe, Alexis Brice, Frédéric Blanc, Philippe Couratier, Mira Didic, Bruno Dubois, Véronique Golfier, Didier Hannequin, Lucette Lacomblez, Isabelle Le Ber, Richard Lévy, Vincent Meininger, Bernard‐François Michel, Florence Pasquier, Catherine Thomas-Antérion, Michèle Puel, François Salachas, François Sellal, Martine Vercelletto,

Parkinson's Disease Mechanisms and Treatments

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.