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.
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.
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.