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Neurogenetics (2008) 9:197205 DOI 10.1007/s10048-008-0127-3
ORIGINAL ARTICLE
Progranulin genetic variations in frontotemporal lobar degeneration: evidence for low mutation frequency in an Italian clinical series
Barbara Borroni & Silvana Archetti &
Antonella Alberici & Chiara Agosti &
Massimo Gennarelli & Barbara Bigni &
Cristian Bonvicini & Maria Ferrari & Giuseppe Bellelli &
Daniela Galimberti & Elio Scarpini & Diego Di Lorenzo &
Luigi Caimi & Carlo Caltagirone & Monica Di Luca &
Alessandro Padovani
Received: 4 December 2007 / Accepted: 12 March 2008 / Published online: 8 April 2008 # Springer-Verlag 2008
Abstract 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 510% of FTLD and for 2025% 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
B. Borroni : A. Alberici : C. Agosti : B. Bigni : A. Padovani Department of Neurology, University of Brescia,Brescia, Italy
S. Archetti : M. Ferrari : D. Di Lorenzo : L. Caimi Laboratory of Biotechnology, Department of Diagnostic of Laboratories, University of Brescia,Brescia, Italy
M. Gennarelli : C. Bonvicini Genetic Unit, IRCCS Brescia, Brescia, Italy
G. BellelliRehabilitation and Geriatric Unit,...