Clinical, genetic, and pathologic characteristics of patients with frontotemporal dementia and progranulin mutations.
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).


METHODS
Retrospective clinical-pathologic study.


METHODS
Academic medical center.


METHODS
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.


METHODS
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.


CONCLUSIONS
Patients with a GRN mutation differ clinically from those with the same pathologic diagnosis but no GRN mutation.
Van Deerlin
Vivianna M
VM
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
Wood
Elisabeth McCarty
EM
Moore
Peachie
P
Yuan
Wuxing
W
Forman
Mark S
MS
Clark
Christopher M
CM
Neumann
Manuela
M
Kwong
Linda K
LK
Trojanowski
John Q
JQ
Lee
Virginia M-Y
VM
Grossman
Murray
M
D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000523:psychology*; D005260:Female; D005625:Frontal Lobe; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D007398:Interpersonal Relations; D007806:Language Disorders / Q000209:etiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000523:psychology; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D010554:Personality Disorders / Q000209:etiology; D000077153:Progranulins; D021641:Recognition, Psychology; D012189:Retrospective Studies; D013702:Temporal Lobe; D025801:Ubiquitin / Q000378:metabolism
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D025801:Ubiquitin