Le Ber, I., de Septenville A., Millecamps S. ... Brice A.
Neurobiology of Aging,
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% to 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 five LoF mutations, in four FTD-ALS and one ALS patients. We also identified five heterozygous missense variants, predicted deleterious, in one isolated FTD, one FTD-ALS and three 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.