title: No major progranulin genetic variability contribution to disease etiopathogenesis in an ALS Italian cohort.
abstract: To analyze the contribution of progranulin (PGRN) to the etiopathogenesis of amyotrophic lateral sclerosis (ALS), we performed a PGRN gene screening in 146 Italian patients (12 familial cases) and evaluated the association of two common variants with risk of developing ALS in 239 sporadic cases (SALS). Progranulin mRNA and protein levels were measured in peripheral blood mononuclear cells and serum of a subset of these patients and controls. PGRN sequence analysis revealed a heterozygous change (p.S120Y), previously observed in an independent sporadic ALS-FTD patient. Haplotype analysis showed a conserved PGRN region among these two subjects consistent with possible common ancestor allele. Two non-coding polymorphisms were not associated to increased risk to develop ALS; mRNA and serum levels were not significantly different between cases and controls. Overall, our data argue against the hypothesis of progranulin as a major risk factor for motor neuron dysfunction, at least in Italian population. The p.S120Y variant may characterize rare patients with SALS, although its pathogenetic mechanism remains to be elucidated.
authors.affiliation: Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico Mangiagalli and Regina Elena, Milan, Italy. roberto.delbo@unimi.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Del Bo
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
authors.forename: Domenico
authors.initials: D
authors.lastname: Santoro
authors.forename: Isabella
authors.initials: I
authors.lastname: Ghione
authors.forename: Chiara
authors.initials: C
authors.lastname: Fenoglio
authors.forename: Serena
authors.initials: S
authors.lastname: Ghezzi
authors.forename: Michela
authors.initials: M
authors.lastname: Ranieri
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Chiara
authors.initials: C
authors.lastname: Briani
authors.forename: Luigi
authors.initials: L
authors.lastname: Murri
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Schymick
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Nereo
authors.initials: N
authors.lastname: Bresolin
authors.forename: Giacomo P
authors.initials: GP
authors.lastname: Comi
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000209:etiology* / Q000235:genetics*; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000235:genetics*; D007558:Italy; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger