• Adriano Chiò, Gabriella Restagno, Maura Brunetti, Irene Ossola, Andrea Calvo, Antonio Canosa, Cristina Moglia, Gianluca Floris, Paolo Tacconi, Francesco Marrosu, Maria Giovanna Marrosu, Maria Rita Murru, Elisa Majounie, Alan E Renton, Yvegeniya Abramzon, Maura Pugliatti, Maria Alessandra Sotgiu, Bryan J Traynor, Giuseppe Borghero, and SARDINIALS Consortium.
• Department of Neuroscience, University of Torino,Torino, Italy. achio@usa.net
• J. Neurol. Neurosurg. Psychiatr. 2012 Jul 1; 83 (7): 730-3.

BackgroundIn the isolated population of Sardinia, a Mediterranean island, ∼25% of ALS cases carry either a p.A382T mutation of the TARDBP gene or a GGGGCC hexanucleotide repeat expansion in the first intron of the C9ORF72 gene.ObjectiveTo describe the co-presence of two genetic mutations in two Sardinian ALS patients.MethodsWe identified two index ALS cases carrying both the p.A382T missense mutation of TARDBP gene and the hexanucleotide repeat expansion of C9ORF72 gene.ResultsThe index case of Family A had bulbar ALS and frontemporal dementia (FTD) at 43. His father, who carried the hexanucleotide repeat expansion of C9ORF72 gene, had spinal ALS and FTD at 64 and his mother, who carried the TARDBP gene p.A382T missense mutation, had spinal ALS and FTD at 69. The index case of Family B developed spinal ALS without FTD at 35 and had a rapid course to respiratory failure. His parents are healthy at 62 and 63. The two patients share the known founder risk haplotypes across both the C9ORF72 9p21 locus and the TARDBP 1p36.22 locus.ConclusionsOur data show that in rare neurodegenerative causing genes can co-exist within the same individuals and are associated with a more severe disease course.

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