• Online Features  This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (20)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Neurology  • Dementias  • Neurogenetics  • Neurology, Other  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Vivianna M. Van Deerlin, MD, PhD; Elisabeth McCarty Wood, MS; Peachie Moore, BA; Wuxing Yuan, MS; Mark S. Forman, MD, PhD; Christopher M. Clark, MD; Manuela Neumann, MD, PhD; Linda K. Kwong, PhD; John Q. Trojanowski, MD, PhD; Virginia M.-Y. Lee, PhD; Murray Grossman, MD

Arch Neurol. 2007;64(8):1148-1153.

Background  Patients with frontotemporal dementia due to mutation of progranulin may have a distinct phenotype.

Objective  To identify distinct clinical and pathologic features of patients with frontotemporal dementia who have mutations of progranulin (GRN).

Design  Retrospective clinical-pathologic study.

Setting  Academic medical center.

Patients  Twenty-eight patients with frontotemporal dementia, including 9 with GRN mutations (4 autopsy cases and 5 with only clinical information) and 19 with the identical pathologic diagnosis—frontotemporal lobar degeneration with ubiquitin-positive and tau-negative inclusions (FTLD-U)—and no GRN mutations.

Main Outcome Measures  Demographic, symptom, neuropsychological, and autopsy characteristics.

Results  Patients with and without a GRN mutation have similar demographic features, although family history is significantly more common in patients with frontotemporal dementia and a GRN mutation. Both patient groups have frequent social and personality complaints. Neuropsychological evaluation reveals a significant recognition memory deficit in patients with a GRN mutation but a significant language deficit only in patients without a GRN mutation. At autopsy, the semiquantitative burden of ubiquitin abnormality is relatively modest in both groups of patients.

Conclusion  Patients with a GRN mutation differ clinically from those with the same pathologic diagnosis but no GRN mutation.

Author Affiliations: Departments of Pathology and Laboratory Medicine (Drs Van Deerlin, Forman, Neumann, Kwong, Trojanowski, and Lee, Mss Wood and Moore, and Mr Yuan) and Neurology (Drs Clark and Grossman and Ms Moore), Center for Neurodegenerative Disease Research (Drs Forman, Neumann, Kwong, Trojanowski, and Lee and Ms Wood), and Alzheimer's Disease Center (Drs Clark, Trojanowski, and Lee), University of Pennsylvania School of Medicine, Philadelphia.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Genetic and Clinical Features of Progranulin-Associated Frontotemporal Lobar Degeneration
Chen-Plotkin et al.
Arch Neurol 2011;68:488-497.
ABSTRACT | FULL TEXT  

TDP-43 subtypes are associated with distinct atrophy patterns in frontotemporal dementia
Rohrer et al.
Neurology 2010;75:2204-2211.
ABSTRACT | FULL TEXT  

The Spectrum of Mutations in Progranulin: A Collaborative Study Screening 545 Cases of Neurodegeneration
Yu et al.
Arch Neurol 2010;67:161-170.
ABSTRACT | FULL TEXT  

Voxel-based morphometry patterns of atrophy in FTLD with mutations in MAPT or PGRN
Whitwell et al.
Neurology 2009;72:813-820.
ABSTRACT | FULL TEXT  

Amyotrophic Lateral Sclerosis-Plus Syndrome With TAR DNA-Binding Protein-43 Pathology
McCluskey et al.
Arch Neurol 2009;66:121-124.
ABSTRACT | FULL TEXT  

Variations in the progranulin gene affect global gene expression in frontotemporal lobar degeneration
Chen-Plotkin et al.
Hum Mol Genet 2008;17:1349-1362.
ABSTRACT | FULL TEXT  

Phenotype variability in progranulin mutation carriers: a clinical, neuropsychological, imaging and genetic study
Le Ber et al.
Brain 2008;131:732-746.
ABSTRACT | FULL TEXT  

TDP-43 Pathologic Lesions and Clinical Phenotype in Frontotemporal Lobar Degeneration With Ubiquitin-Positive Inclusions
Grossman et al.
Arch Neurol 2007;64:1449-1454.
ABSTRACT | FULL TEXT