title: The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms.
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.
authors.affiliation: Centro per i Disordini del Movimento, Dipartimento di Scienze Cardiovascolari e Neurologiche, Sezione Neurologia, Policlinico Universitario, Università di Cagliari, SS 554 Bivio Sestu, 09042 Monserrato, Cagliari, Italy. antonino.cannas@tiscali.it
authors.forename: Antonino
authors.initials: A
authors.lastname: Cannas
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borghero
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Floris
authors.forename: Paolo
authors.initials: P
authors.lastname: Solla
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Elisa
authors.initials: E
authors.lastname: Majounie
authors.forename: Emanuela
authors.initials: E
authors.lastname: Costantino
authors.forename: Valeria
authors.initials: V
authors.lastname: Piras
authors.forename: Loredana
authors.initials: L
authors.lastname: Lavra
authors.forename: Carla
authors.initials: C
authors.lastname: Pani
authors.forename: Gianni
authors.initials: G
authors.lastname: Orofino
authors.forename: Francesca
authors.initials: F
authors.lastname: Di Stefano
authors.forename: Paolo
authors.initials: P
authors.lastname: Tacconi
authors.forename: Marcello Mario
authors.initials: MM
authors.lastname: Mascia
authors.forename: Antonella
authors.initials: A
authors.lastname: Muroni
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Murru
authors.forename: Stefania
authors.initials: S
authors.lastname: Tranquilli
authors.forename: Daniela
authors.initials: D
authors.lastname: Corongiu
authors.forename: Marcella
authors.initials: M
authors.lastname: Rolesu
authors.forename: Stefania
authors.initials: S
authors.lastname: Cuccu
authors.forename: Francesco
authors.initials: F
authors.lastname: Marrosu
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Marrosu
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D010641:Phenotype
chemical_list: D004268:DNA-Binding Proteins
references.citation: J Neuropathol Exp Neurol. 2008 Dec;67(12):1159-65
references.pmid: 19018245
references.citation: Neurogenetics. 2011 Aug;12(3):203-9
references.pmid: 21667065
references.citation: Neurology. 2008 Aug 26;71(9):670-6
references.pmid: 18725592
references.citation: Arch Neurol. 1999 Jan;56(1):33-9
references.pmid: 9923759
references.citation: Am J Pathol. 2007 Jul;171(1):227-40
references.pmid: 17591968
references.citation: Curr Opin Neurobiol. 2007 Oct;17(5):548-55
references.pmid: 17936612
references.citation: Acta Neuropathol. 2010 Jul;120(1):55-66
references.pmid: 20512649
references.citation: Neurodegener Dis. 2010;7(4):260-4
references.pmid: 20197650
references.citation: Neurobiol Aging. 2011 Dec;32(12):2327.e1-5
references.pmid: 21803454
references.citation: Science. 2006 Oct 6;314(5796):130-3
references.pmid: 17023659
references.citation: Brain Res. 2007 Dec 12;1184:284-94
references.pmid: 17963732
references.citation: Neurology. 1996 Jul;47(1):1-9
references.pmid: 8710059
references.citation: Parkinsonism Relat Disord. 2009 May;15(4):277-80
references.pmid: 18805725
references.citation: Neuropathology. 2010 Apr;30(2):103-12
references.pmid: 20102519
references.citation: Acta Neuropathol. 2004 Nov;108(5):379-85
references.pmid: 15351890
references.citation: Neurobiol Aging. 2012 Aug;33(8):1846.e1-4
references.pmid: 22398199
references.citation: Clin Genet. 2012 Feb;81(2):172-8
references.pmid: 21418058
references.citation: Acta Neurol Scand. 2013 Apr;127(4):251-9
references.pmid: 22881448
references.citation: J Neuropathol Exp Neurol. 2008 Jun;67(6):555-64
references.pmid: 18520774
references.citation: Int J Mol Sci. 2009 Jan;10(1):232-46
references.pmid: 19333444
references.citation: Acta Neuropathol. 2007 Sep;114(3):221-9
references.pmid: 17653732
references.citation: Neurology. 2005 Dec 27;65(12):1863-72
references.pmid: 16237129
references.citation: Arch Neurol. 2011 May;68(5):594-8
references.pmid: 21220647
references.citation: Neurology. 1990 Aug;40(8):1203-12
references.pmid: 2381527