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). 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.