Abstract
Recently, mutations in the progranulin gene (GRN) were reported to account for the vast majority of Frontotemporal lobar Degeneration (FTLD) and a growing number of reports describe the implication of this gene in the development of the FTLD pathology with a significant variation in clinical features. To better clarify the contribution of GRN mutations to Italian FTLD, we screened 381 subjects: 171 cases and 210 healthy subjects, all from Central Italy, particularly of Tuscan origins. GRN gene was analyzed using High Resolution Melting Analysis and automated Genetic Analyzer. Human Progranulin ELISA Kit was employed to determine the plasma progranulin levels. The screening showed a total of six genetic variants in the GRN gene: 3 pathogenic and 3 non pathogenic in 13 out of 171 patients. The rare intronic variant IVS2 +7 G > A was found in one patient. The pathogenetic mutation, p.T272SfsX10, is confirmed as the most common GRN mutation in Italian FTLD patients with a frequency in our study of 2.32%. Moreover, we identified the first Italian patient with the p.R493X mutation, to date described in 43 families worldwide. Our data report, for the first time, the occurrence of GRN mutations in Tuscany, Central Italy, confirming that genetic variations in this gene could be a considerable genetic cause of FTLD and that genetic screening might be useful both in familial and sporadic FTLD patients.