%0 Journal Article %T C9ORF72 repeat expansions in the frontotemporal dementias spectrum of diseases: a flow-chart for genetic testing. %+ Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM) %+ Génétique du cancer et des maladies neuropsychiatriques (GMFC) %+ Laboratoire d'Imagerie Fonctionnelle (LIF) %+ Neurologie générale et maladies inflammatoires du système nerveux [Toulouse] %+ Imagerie cérébrale et handicaps neurologiques (ICHN) %+ Troubles cognitifs vasculaires et dégénératifs - EA 2691 (TCDV) %+ Neurologie et thérapeutique expérimentale %+ Service de neurologie [Nantes] %+ Neuroépidémiologie Tropicale (NET) %+ Service de Neurologie [CHU Limoges] %+ Service de neurologie %+ Département de neurologie [Lille] %+ CHU Pitié-Salpêtrière [AP-HP] %+ Centre de Mémoire de Ressource et Recherche (CMRR) %+ Service de neurologie et de neuropsychologie %+ The Mediterranean Institute of Neurobiology %+ Physiologie et physiopathologie de la motricité chez l'homme %+ Service de Neurologie [Strasbourg] %+ Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier] (SLA CHRU Montpellier) %+ Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon) %+ Department of Experimental Cardiology %+ UMR 1253 iBrain Imagerie et cerveau (iBrain) %+ Service de génétique médicale %+ Estrogènes, Expression génique et pathologies du Système Nerveux Central - UFC (E2SNC / ESTROGENES) %A Le Ber, Isabelle %A Camuzat, Agnès %A Guillot-Noel, Lena %A Hannequin, Didier %A Lacomblez, Lucette %A Golfier, Véronique %A Puel, Michèle %A Martinaud, Olivier %A Deramecourt, Vincent %A Rivaud-Pechoux, Sophie %A Millecamps, Stéphanie %A Vercelletto, Martine %A Couratier, Philippe %A Sellal, François %A Pasquier, Florence %A Salachas, François %A Thomas-Antérion, Catherine %A Didic, Mira %A Pariente, Jérémie %A Seilhean, Danielle %A Ruberg, Merle %A Wargon, Isabelle %A Blanc, Frédéric %A Camu, William %A Michel, Bernard-François %A Berger, Eric %A Sauvée, Mathilde %A Thauvin-Robinet, Christel %A Mondon, Karl %A Tournier-Lasserve, Elisabeth %A Goizet, Cyril %A Fleury, Marie %A Viennet, Gabriel %A Verpillat, Patrice %A Meininger, Vincent %A Duyckaerts, Charles %A Dubois, Bruno %A Brice, Alexis %< avec comité de lecture %@ 1387-2877 %J Journal of Alzheimer's Disease %I IOS Press %V 34 %N 2 %P 485-99 %8 2013-01-01 %D 2013 %R 10.3233/JAD-121456 %M 23254636 %Z Life Sciences [q-bio]/Santé publique et épidémiologieJournal articles %X Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion. C9ORF72 expansions were much more frequent in the large subgroup of patients with familial FTD-ALS (65.9%) than in those with pure FTD (12.8%); they were even more frequent than in familial pure ALS, according to estimated frequencies in the literature (23-50%). The frequency of carriers in non-familial FTD-ALS (12.7%) indicates that C9ORF72 should be analyzed even when family history is negative. Mutations were detected in 6.8% of PPA patients, and in 3.2% of patients with a clinical phenotype of PSP, thus enlarging the phenotype spectrum of C9ORF72. Onset was later in C9ORF72 (57.4 years, 95%CI: 55.9-56.1) than in MAPT patients (46.8, 95%CI: 43.0-50.6; p = 0.00001) and the same as in PGRN patients (59.6 years; 95%CI: 57.6-61.7; p = 0.4). ALS was more frequent in C9ORF72 than in MAPT and PGRN patients; onset before age 50 and parkinsonism were indicative of MAPT mutations, whereas hallucinations were indicative of PGRN mutations; prioritization of genetic testing is thus possible. Penetrance was age- and gender-dependent: by age 50, 78% of male carriers were symptomatic, but only 52% of females. This can also guide genetic testing and counseling. A flowchart for genetic testing is thus proposed. %G English %L hal-00924796 %U https://unilim.hal.science/hal-00924796 %~ UNILIM %~ UNIV-NANTES %~ UPMC %~ UNIV-TLSE2 %~ UNIV-TLSE3 %~ UNIV-TOURS %~ CNRS %~ UNIV-AMU %~ UNIV-FCOMTE %~ UNIV-MONTP1 %~ APHP %~ NET %~ SANTE_PUB_INSERM %~ E2SNC %~ UPMC-LIF %~ GEIST %~ LIB %~ ICM %~ COMUE-NORMANDIE %~ UPMC_POLE_1 %~ UPMC_POLE_4 %~ UNIV-MONTPELLIER %~ UNIROUEN %~ SORBONNE-UNIVERSITE %~ SU-INF-2018 %~ SU-MEDECINE %~ SU-SCIENCES %~ SU-MED %~ ALLIANCE-SU %~ EPIMACT %~ OMEGAHEALTH %~ NANTES-UNIVERSITE %~ UNIV-NANTES-AV2022 %~ UNIV-UT3 %~ UT3-INP %~ UT3-TOULOUSEINP %~ UM1-UM2 %~ LABCIS