A novel homozygous mutation in TBK1 gene causing ALS-FTD

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that leads to death in 3-5 years. In up to 10% of cases there is a family history for ALS. Several genes have been associated with ALS and many of them are also involved in the development of Fronto-temporal dementia (FTD). Recently mutations in the TANK binding kinase 1 (TBK1) have been identified as a cause of ALS and FTD. Most TBK1 known mutations associated with ALS are nonsense and frameshift mutations, resulting in premature termination codons (TCs), causing the production of an incomplete and non-functional protein. Here we described a case of ALS associated with bv-FTD of a woman with a novel homozygous missense mutation in TBK1 gene. We used a silico computational software to evaluate the effect of this novel mutation and this analysis indicated, with high probability a detrimental effect of protein expression and activity of TBK1. The haploinsufficiency due to the homozygous mutations probably led to the development of ALS-FTD in this patient.