TY - JOUR
T1 - Progranulin genetic variations in frontotemporal lobar degeneration
T2 - Evidence for low mutation frequency in an Italian clinical series
AU - Borroni, Barbara
AU - Archetti, Silvana
AU - Alberici, Antonella
AU - Agosti, Chiara
AU - Gennarelli, Massimo
AU - Bigni, Barbara
AU - Bonvicini, Cristian
AU - Ferrari, Maria
AU - Bellelli, Giuseppe
AU - Galimberti, Daniela
AU - Scarpini, Elio
AU - Di Lorenzo, Diego
AU - Caimi, Luigi
AU - Caltagirone, Carlo
AU - Di Luca, Monica
AU - Padovani, Alessandro
PY - 2008/7
Y1 - 2008/7
N2 - 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.
AB - 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.
KW - Frequency
KW - Frontotemporal lobar degeneration
KW - Mutations
KW - Progranulin
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U2 - 10.1007/s10048-008-0127-3
DO - 10.1007/s10048-008-0127-3
M3 - Article
C2 - 18392865
AN - SCOPUS:46149083470
VL - 9
SP - 197
EP - 205
JO - Neurogenetics
JF - Neurogenetics
SN - 1364-6745
IS - 3
ER -