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

Dementia and Geriatric Cognitive Disorders
Eoin P FlanaganKeith A Josephs

Abstract

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. 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). 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). 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 co...Continue Reading

Citations

Mar 5, 2016·NeuroImage. Clinical·Jennifer L WhitwellKeith A Josephs
Nov 10, 2015·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·A PilottoD Berg
May 12, 2016·Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration·Francesca Di StefanoGianluca Floris
Apr 23, 2016·Journal of Alzheimer's Disease : JAD·Amy BrodtmannAdam P Vogel
Apr 16, 2017·Neurologic Clinics·Nicholas T OlneyBruce L Miller
Feb 2, 2019·Continuum : Lifelong Learning in Neurology·Hugo Botha, Keith A Josephs
Jan 2, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Eliana Marisa RamosGiovanni Coppola
May 2, 2020·The Journal of Orthopaedic and Sports Physical Therapy·Rasmus Østergaard NielsenEvert Verhagen
Sep 25, 2015·Journal of Alzheimer's Disease : JAD·Charles R MarshallNick C Fox
May 20, 2018·Nature Reviews. Neurology·Sara Van MosseveldeChristine Van Broeckhoven
Oct 20, 2020·Journal of Alzheimer's Disease : JAD·Marjut HaapanenEino Solje
Feb 23, 2021·Journal of Alzheimer's Disease : JAD·Vanesa PytelJordi A Matias-Guiu
Jul 6, 2021·Aphasiology·Joseph R DuffyKeith A Josephs
May 14, 2021·Neurology·Dario SaracinoUNKNOWN French Research Network on FTD/FTD-ALS

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