Studio genetico della sclerosi laterale amiotrofica in Sardegna

Aims: This study is part of an ongoing and broader epidemiological research on ALS, aimed to disclose population-specific clinical and genetic variants of ALS in Sardinia. The study is carried out in collaboration with the University of Turin (Prof. Adriano Chiò and coll.) and the Unit of Neurology, Cagliari Health District (Dr. Giuseppe Borghero and coll.).Methods: Sardinian ALS patients and controls, identified in the period 2008-2013, were included in the study and screened for TARDBP, C9ORF72, SOD1, and FUS mutations.Results: Genetic mutations were identified in 155 cases (41.3%), in 74% of familial ALS (fALS) and in 30% of apparently sporadic ALS patients (sALS), mostly the p.A382T mutation of TARDBP (20.8%) and the C9ORF72 (13.6%). Some patients carried the double mutations p.A382T and p.G295S of TARDBP (0.3%) and both C9ORF72 and p.A382T of TARDBP (2.1%). Mutation of TARDBP was more frequent among sALS patients, while C9ORF72 mutation recurred more among fALS cases. Subjects carrying the C9ORF72 mutation had a higher frequency of FTD, bulbar-onset disease and a shorter survival. Patients with both C9ORF72 and the TARDBP p.A382T mutation had a significantly lower age at onset. ALS patients carrying the p.A382T and the p.G295S TARDBP mutations share different haplotypes across these loci.Conclusions: Genetic mutations were identified in more than 40% of patients, higher than in other Caucasian populations, suggesting Sardinian type of ALS with its own behavior.