Loss-of-function mutations in the gene encoding for the protein progranulin 
(PGRN), GRN, are one of the major genetic abnormalities involved in 
frontotemporal lobar degeneration. However, genetic variations, mainly missense, 
in GRN have also been linked to other neurodegenerative diseases. We found 12 
different pathogenic/likely pathogenic variants in 21 patients identified in a 
cohort of Italian patients affected by various neurodegenerative disorders. We 
detected the p.Thr272SerfsTer10 as the most frequent, followed by the 
c.1179+3A>G variant. We characterized the clinical phenotype of 12 patients from 
3 pedigrees carrying the c.1179+3A>G variant, demonstrated the pathogenicity of 
this mutation, and detected other rarer variants causing haploinsufficiency 
(p.Met1?, c.709-2A>T, p.Gly79AspfsTer39). Finally, by applying bioinformatics, 
neuropathological, and biochemical studies, we characterized 6 
missense/synonymous variants (p.Asp94His, p.Gly117Asp, p.Ala266Pro, p.Val279Val, 
p.Arg298His, p.Ala505Gly), including 4 previously unreported. The designation of 
variants is crucial for genetic counseling and the enrollment of patients in 
clinical studies.