Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders

Serena Lattante, Stéphanie Millecamps, Giovanni Stevanin, Sophie Rivaud-Péchoux, Carine Moigneu, Agnès Camuzat, Sandra Da Barroca, Emeline Mundwiller, Philippe Couarch, François Salachas, Didier Hannequin, Vincent Meininger, Florence Pasquier, Danielle Seilhean, Philippe Couratier, Véronique Danel-Brunaud, Anne-Marie Bonnet, Christine Tranchant, Eric Le Guern, Alexis BriceIsabelle Le Ber, Edor Kabashi

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

50 Citazioni (Scopus)


OBJECTIVE: The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion. METHODS: We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS). RESULTS: We found a significant association with intermediate repeat size (≥29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate ATXN2 repeat length. ATXN2 repeat lengths in patients with PSP and FTD were found to be similar to the controls. CONCLUSIONS: ATXN2 intermediary repeat length is a strong risk factor for ALS and FTD-ALS. Furthermore, we propose that ATXN2 polyQ expansions could act as a strong modifier of the FTD phenotype in the presence of a C9orf72 repeat expansion, leading to the development of clinical signs featuring both FTD and ALS.
Lingua originaleEnglish
pagine (da-a)990-995
Numero di pagine6
Stato di pubblicazionePubblicato - 2014


  • Amyotrophic Lateral Sclerosis
  • DNA Repeat Expansion
  • Frontotemporal Dementia
  • Risk Factors
  • Supranuclear Palsy, Progressive


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