Frontotemporal lobar degeneration (FTLD) is a genetically heterogenous syndrome 
and has been associated most recently with a hexanucleotide repeat expansion 
within the C9ORF72 gene. Pathogenic TDP-43 gene (TARDBP) mutations have been 
identified in amyotrophic lateral sclerosis, but the role of TARDBP mutations in 
FTLD is more contradictory. To investigate the role of TARDBP mutations in a 
clinical series of Finnish FTLD patients, we sequenced TARDBP exons 1 to 6 in 77 
FTLD patients. No evident pathogenic mutations were found. We identified a novel 
heterozygous c.876_878delCAG sequence variant in 2 related patients with 
behavioral variant frontotemporal dementia without amyotrophic lateral 
sclerosis. The variant is predicted to cause an amino acid deletion of serine at 
position 292 (p.Ser292del). However, p.Ser292del was also found in 1 healthy 
middle-aged control. Interestingly, both patients carried the C9ORF72 expansion. 
Therefore, the TARDBP variant p.Ser292del might be considered a rare 
polymorphism and the C9ORF72 repeat expansion the actual disease-causing 
mutation in the family. Our results suggest that TARDBP mutations are a rare 
cause of FTLD. However, the interaction of several genetic factors needs to be 
taken into account when investigating neurodegenerative diseases.