There are three major associated clinical syndromes, behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA); three principal histologies, involving tau, TDP-43 and FUS proteins; and mutations in three major genes, MAPT, GRN and C9orf72, along with several other less common gene mutations.
In the case of the MAPT mutation, the family presented with both bvFTD and PNFA phenotypes, while the VCP mutation was also related to an early-onset AD phenotype.
As a result, 2 novel mutations in MAPT (p.D177V and p.P513A) were identified in a sporadic and familial patient with PNFA respectively, and one known mutation in MAPT (p.N279K) was detected in an FTD-parkinsonism family.
The V363I mutation of the microtubule-associated protein tau gene has previously been associated with a case of primary progressive nonfluent aphasia with variable penetrance.