Borroni B, Archetti S, Alberici A, Agosti C, Gennarelli M, Bigni B, Bonvicini C, Ferrari M, Bellelli G, Galimberti D, Scarpini E, Di Lorenzo D, Caimi L, Caltagirone C, Di Luca M, and Padovani A
Frontotemporal lobar degeneration (FTLD) recognises high familial incidence, with up to 50% of patients reported to have a family history of similar dementia. It has been reported that mutations within progranulin (PGRN) gene are a major cause of FTLD in the USA and worldwide, counting for 5-10% of FTLD and for 20-25% of familiar FTLD cases. The aim of the present study was to define the role of PGRN genetic variations in a large sample of consecutive patients with FTLD in Italy. Two-hundred forty-three FTLD patients were investigated. Each subject performed a clinical and neuropsychological evaluation, a functional and structural brain imaging, and the diagnosis was confirmed by at least 1 year follow-up. PGRN sequencing was performed in all FTLD patients and in 121 healthy age-matched controls drawn from the same geographic area. Only one PGRN pathogenetic mutation was found, consisting of a four-base pair deletion in the coding sequence of exon 8 (delCACT). This mutation was recognised in four patients, being the overall frequency of mutations in our clinical series of 1.64%. Considering only patients with a well-known family history for dementia, the frequency of this mutation was 6%. Moreover, four missense mutations within intron regions (g.100474G>A, g.100674G>A, g.101266G>A, g.102070G>A) were found. The frequency of these genetic variations did not differ in patients compared to controls, and they did not influence on clinical FTLD phenotype. In conclusion, this study supports a lower frequency of PGRN mutations amongst FTLD patients in Italy compared to literature data and further underlies the genetic heterogeneity of FTLD.