Abstract
Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.
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Acknowledgments
The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 259867. This work was supported in part by the Intramural Research Programs of the NIH, National Institute on Aging (Z01-AG000949-02).
Disclosures
Dr. Chiò serves on the editorial advisory board of Amyotrophic Lateral Sclerosis and has received research support from the Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), Italian Ministry of University and Research, University of Torino, Federazione Italiana Giuoco Calcio, and European Commission (Health Seventh Framework Programme); he serves on a scientific advisory board for Biogen Idec. Dr. Bryan J. Traynor is on the editorial board for the journal Neurology and has received research support from the ALS Association, the Packard Center for ALS Research, Microsoft Research, the Myasthenia Gravis Foundation, and Italiana Giuoco Calcio (FIGC). Dr. Calvo has received research support from Regione Piemonte (Ricerca Finalizzata) and Compagnia di San Paolo. All other authors report no disclosures.
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Antonino Cannas, Giuseppe Borghero, Gian Luca Floris, Paolo Solla, Adriano Chiò, and Bryan J. Traynor contributed equally to the study.
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Cannas, A., Borghero, G., Floris, G.L. et al. The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms. Neurogenetics 14, 161–166 (2013). https://doi.org/10.1007/s10048-013-0360-2
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DOI: https://doi.org/10.1007/s10048-013-0360-2