Dominant frontotemporal dementia mutations in 140 cases of primary progressive aphasia and speech apraxia

Eoin P. Flanagan, Matthew C. Baker, Ralph B. Perkerson, Joseph R. Duffy, Edythe A. Strand, Jennifer L. Whitwell, Mary M. MacHulda, Rosa Rademakers, Keith A. Josephs

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Mutations in three genes [chromosome 9 open-reading-frame 72 (C9ORF72); microtubule-associated protein tau (MAPT) and progranulin (GRN)] 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. Methods: We therefore assessed for genetic mutations in C9ORF72, MAPT and GRN 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). Results: 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: MAPT (n = 0), GRN (n = 3) and C9ORF72 (n = 2). Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)281-286
Number of pages6
JournalDementia and geriatric cognitive disorders
Issue number5-6
StatePublished - May 28 2015


  • Apraxia of speech
  • C9ORF72
  • Genetics
  • Logopenic progressive aphasia
  • MAPT
  • PPA
  • Progranulin
  • Progressive nonfluent aphasia
  • Semantic dementia

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Cognitive Neuroscience
  • Psychiatry and Mental health


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