No major progranulin genetic variability contribution to disease etiopathogenesis in an ALS Italian cohort

• Published in: Neurobiology of aging 2011-06, Vol.32 (6), p.1157-1158
• Main Authors: Del Bo, Roberto, Corti, Stefania, Santoro, Domenico, Ghione, Isabella, Fenoglio, Chiara, Ghezzi, Serena, Ranieri, Michela, Galimberti, Daniela, Mancuso, Michelangelo, Siciliano, Gabriele, Briani, Chiara, Murri, Luigi, Scarpini, Elio, Schymick, Jennifer C, Traynor, Bryan J, Bresolin, Nereo, Comi, Giacomo P
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - etiology; Amyotrophic Lateral Sclerosis - genetics; Biological and medical sciences; Cohort Studies; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Development. Senescence. Regeneration. Transplantation; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Genetic risk factor; Genotype; Humans; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Internal Medicine; Italy; Medical sciences; Mutation - genetics; Neurology; Progranulin; Progranulins; RNA, Messenger - metabolism; Susceptibility; Vertebrates: nervous system and sense organs
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2009.06.006

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.