No major progranulin genetic variability contribution to disease etiopathogenesis in an ALS Italian cohort.
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.
Del Bo
Roberto
R
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
Corti
Stefania
S
Santoro
Domenico
D
Ghione
Isabella
I
Fenoglio
Chiara
C
Ghezzi
Serena
S
Ranieri
Michela
M
Galimberti
Daniela
D
Mancuso
Michelangelo
M
Siciliano
Gabriele
G
Briani
Chiara
C
Murri
Luigi
L
Scarpini
Elio
E
Schymick
Jennifer C
JC
Traynor
Bryan J
BJ
Bresolin
Nereo
N
Comi
Giacomo P
GP
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
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger