Erschienen in:
01.05.2013 | Original Article
The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms
verfasst von:
Antonino Cannas, Giuseppe Borghero, Gian Luca Floris, Paolo Solla, Adriano Chiò, Bryan J. Traynor, Andrea Calvo, Gabriella Restagno, Elisa Majounie, Emanuela Costantino, Valeria Piras, Loredana Lavra, Carla Pani, Gianni Orofino, Francesca Di Stefano, Paolo Tacconi, Marcello Mario Mascia, Antonella Muroni, Maria Rita Murru, Stefania Tranquilli, Daniela Corongiu, Marcella Rolesu, Stefania Cuccu, Francesco Marrosu, Maria Giovanna Marrosu
Erschienen in:
Neurogenetics
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Ausgabe 2/2013
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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.