Eoin P. Flanagan1, Matthew Baker2, Ralph B. Perkerson2, Joseph R. Duffy3, Edythe A. Strand3, Jennifer L. Whitwell4, Mary M. Machulda5, Rosa Rademakers2, Keith A. Josephs1
1Behavioral Neurology and
2Department of Neuroscience, Mayo Clinic, Jacksonville, Fla., USA
3Speech Pathology, Department of Neurology, and Departments of
4Radiology and
5Psychiatry and Psychology, Mayo Clinic, Rochester, Minn., and
Tóm tắt
<b><i>Background:</i></b> Mutations in three genes [chromosome 9 open-reading-frame 72 <i>(C9ORF72)</i>; microtubule-associated protein tau <i>(MAPT)</i> and progranulin <i>(GRN)</i>] account for the vast majority of familial, and a proportion of sporadic, frontotemporal dementia (FTD) cases. Progressive apraxia of speech (PAOS) is a type of FTD characterized by speech production deficits without a known cause. <b><i>Methods:</i></b> We therefore assessed for genetic mutations in <i>C9ORF72</i>, <i>MAPT</i> and <i>GRN</i> in 40 prospectively recruited PAOS patients. For comparison, we also assessed these mutations in 100 patients with primary progressive aphasia (PPA), including logopenic PPA (n = 54), nonfluent/agrammatic PPA (n = 17), semantic PPA (n = 16), and unclassifiable PPA (n = 13). <b><i>Results:</i></b> The mean age at onset of PAOS patients was 66.7 years (± 9.3); 50% were women. Ten patients (25%) had ≥1 first-degree relative with a neurodegenerative disease. No mutations were found in any PAOS patient. In comparison, 36% of the PPA patients had a family history and 5 (5%) had a genetic mutation detected: <i>MAPT</i> (n = 0), <i>GRN</i> (n = 3) and <i>C9ORF72</i> (n = 2). <b><i>Conclusions:</i></b> Although limited by an overrepresentation of logopenic PPA, which frequently predicts Alzheimer's disease pathology, this study suggests that mutations in the three genes most commonly associated with FTD are not associated with PAOS and are not commonly associated with PPA.
