Understanding of frontotemporal lobar degeneration, the underlying pathology 
most often linked to the clinical diagnosis of frontotemporal dementia, is 
rapidly increasing. Mutations in 7 known genes (MAPT, GRN, C9orf72, VCP, CHMP2B, 
and, rarely, TARDBP and FUS) are associated with frontotemporal dementia, and 
the pathologic classification of frontotemporal lobar degeneration has recently 
been modified to reflect these discoveries. Mutations in one of these genes 
(GRN), which encodes progranulin, have been implicated in up to a quarter of 
cases of frontotemporal lobar degeneration with TDP-43 (TAR DNA-binding protein 
43)-positive inclusions; currently, there are more than 60 known pathogenic 
mutations of the gene. We present the clinical, pathologic, and genetic findings 
on 6 cases from 4 families, 5 of which were shown to have a novel GRN 
c.708+6_+9delTGAG mutation.