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Clinical, Genetic, and Pathologic Characteristics of Patients With Frontotemporal Dementia and Progranulin Mutations
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.
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