Corticobasal syndrome associated with the A9D Progranulin mutation.

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 [F]fluorodeoxyglucose-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'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.

• Authors: Salvatore Spina, Jill R Murrell, Edward D Huey, Eric M Wassermann, Pietro Pietrini, Jordan Grafman, Bernardino Ghetti
• Journal: Journal of neuropathology and experimental neurology (J Neuropathol Exp Neurol) Vol. 66 Issue 10 Pg. 892-900 (Oct 2007) ISSN: 0022-3069 [Print] England
• PMID: 17917583 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)

Chemical References

• DNA-Binding Proteins
• GRN protein, human
• Intercellular Signaling Peptides and Proteins
• Progranulins
• Fluorodeoxyglucose F18
• DNA

Topics

• Alleles
• Apraxias (genetics, pathology, psychology)
• Brain (pathology)
• Cognition Disorders (genetics, pathology, psychology)
• DNA (genetics)
• DNA-Binding Proteins (genetics)
• Dementia (genetics, pathology, psychology)
• Fluorodeoxyglucose F18
• Humans
• Intercellular Signaling Peptides and Proteins (genetics)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Neuropsychological Tests
• Positron-Emission Tomography
• Progranulins
• Reverse Transcriptase Polymerase Chain Reaction
• Syndrome