eprintid: 3161 rev_number: 5 eprint_status: archive userid: 69 dir: disk0/00/00/31/61 datestamp: 2016-02-29 10:04:56 lastmod: 2016-02-29 10:04:56 status_changed: 2016-02-29 10:04:56 type: article metadata_visibility: show creators_name: Spina, Salvatore creators_name: Murrell, Jill R. creators_name: Huey, Edward D. creators_name: Wassermann, Eric M. creators_name: Pietrini, Pietro creators_name: Grafman, Jordan creators_name: Ghetti, Bernardino creators_id: creators_id: creators_id: creators_id: creators_id: pietro.pietrini@imtlucca.it creators_id: creators_id: title: Corticobasal Syndrome Associated With the A9D Progranulin Mutation ispublished: pub subjects: RC0321 divisions: CSA full_text_status: none keywords: Alien limb; Apraxia; Frontotemporal lobar degeneration; Hemineglect; Parietal lobe; Progranulin; TDP-43 note: Fulltext available online abstract: Corticobasal syndrome is characterized by cortical dysfunction and L-dopa-unresponsive Parkinsonism, with asymmetrical onset of clinical presentation and evidence of atrophy and/or hypometabolism at neuroimaging. Recently, the heterogeneous pathologic substrate of corticobasal syndrome has been further expanded to include cases with pathologic diagnosis of frontotemporal lobar degeneration with ubiquitin/TDP-43 (TAR DNA binding protein 43)-positive inclusions associated with progranulin (PGRN) mutations. We report a family in which several individuals have been affected with a dementia/movement disorder phenotype. The proband presented at age 45 with spontaneous left arm levitation, ideational apraxia, asymmetric parkinsonism, and dystonia. Subsequently, he developed limb-kinetic apraxia, left-side hemineglect, memory loss, and executive dysfunction. Magnetic resonance imaging and 18Ffluorodeoxyglucose-positron emission tomography studies revealed severe cerebral cortical atrophy and hypometabolism, which were significantly more pronounced in the parietal lobes (right \> left). Neuropathologic examination displayed the highest degree of degeneration and ubiquitin/TDP-43 pathology in the proband{\textquoteright}s parietal areas. Genetic analysis revealed the presence of the c.26C\>A PGRN mutation in 1 allele. This mutation has been reported in association with hereditary-dysphasic-disinhibition-dementia, Alzheimer-like dementia, progressive supranuclear palsy, and primary progressive aphasia. The peculiar findings observed in this patient indicate that the parietal lobe may represent the most vulnerable anatomical area in some of the PGRN-associated frontotemporal lobar degeneration with ubiquitin/TDP-43-positive inclusion cases. date: 2007 date_type: published publication: Journal of Neuropathology and Experimental Neurology volume: 66 number: 10 publisher: The Oxford University Press pagerange: 892-900 id_number: 10.1097/nen.0b013e3181567873 refereed: TRUE issn: 0022-3069 official_url: http://jnen.oxfordjournals.org/content/66/10/892 citation: Spina, Salvatore and Murrell, Jill R. and Huey, Edward D. and Wassermann, Eric M. and Pietrini, Pietro and Grafman, Jordan and Ghetti, Bernardino Corticobasal Syndrome Associated With the A9D Progranulin Mutation. Journal of Neuropathology and Experimental Neurology, 66 (10). pp. 892-900. ISSN 0022-3069 (2007)