Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers
Year: 2018
Type: article
Study design: Observational Study
Abstract: A (GGGGCC)n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10e−4) but our results suggested that the association was mainly driven by age at collection (p < 10e−4). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers.
Source: Neurobiology of Aging
Authors: Clémence Fournier, Mathieu Barbier, Agnès Camuzat, Vincent Anquetil, Serena Lattante, Fabienne Clot, Cécile Cazeneuve, Daisy Rinaldi, Philippe Couratier, Vincent Deramecourt, Mario Sabatelli, Serge Belliard, Martine Vercelletto, Sylvie Forlani, Ludmila Jornea, Alexis Brice, Sophie Auriacombe, Serge Belliard, Frédéric Blanc, Claire Bouteleau-Bretonnière, Mathieu Ceccaldi, Philippe Couratier, Mira Didic, Bruno Dubois, Charles Duyckaerts, Frédérique Etcharry-Bouix, Véronique Golfier, Didier Hannequin, Lucette Lacomblez, Isabelle Le Ber, Richard Levy, Bernard-François Michel, Florence Pasquier, Catherine Thomas-Anterion, Jérémie Pariente, François Sellal, Martine Vercelletto, Eve Benchetrit, Hugo Bertin, Anne Bertrand, Anne Bissery, Stéphanie Bombois, Marie-Paule Boncoeur, Pascaline Cassagnaud, Mathieu Chastan, Yaohua Chen, Marie Chupin, Olivier Colliot, Philippe Couratier, Xavier Delbeucq, Vincent Deramecourt, Christine Delmaire, Emmanuel Gerardin, Claude Hossein-Foucher, Bruno Dubois, Marie-Odile Habert, Didier Hannequin, Géraldine Lautrette, Thibaud Lebouvier, Isabelle Le Ber, Stéphane Lehéricy, Benjamin Le Toullec, Richard Levy, Kelly Martineau, Marie-Anne Mackowiak, Jacques Monteil, Florence Pasquier, Grégory Petyt, Pierre-François Pradat, Assi-Hervé Oya, Daisy Rinaldi, Adeline Rollin-Sillaire, François Salachas, Sabrina Sayah, David Wallon, Eric Leguern, Alexis Brice, Isabelle Le Ber
Institutions: Centre National de la Recherche Scientifique, Inserm, Institut des Sciences Moléculaires, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Institut du Cerveau, Université Pierre-et-Marie-Curie, Sorbonne Université, École Pratique des Hautes Études, Université Paris Sciences et Lettres, Università Cattolica del Sacro Cuore, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, Centre Hospitalier Universitaire de Limoges, Hôpital Universitaire Dupuytren, Épidémiologie des maladies chroniques en zone tropicale, Université de Limoges, Université de Lille, Centre Hospitalier Universitaire de Lille, Lille Neurosciences & Cognition, LabEx DISTALZ, Hôpital Pontchaillou, Centre Hospitalier Universitaire de Rennes, Centre Hospitalier Universitaire de Nantes, Centre d'Investigation Clinique de Nantes, Université de Nantes, Nantes Université, Centre Hospitalier Universitaire de Bordeaux, Laboratoire des Sciences de l'Ingénieur, de l'Informatique et de l'Imagerie, Hôpitaux Universitaires de Strasbourg, Assistance Publique Hôpitaux de Marseille, Institut de Neurosciences des Systèmes, Centre Hospitalier Universitaire d'Angers, Hôpital Sainte-Marguerite, Centre Hospitalier Universitaire de Toulouse, Hôpital Purpan, Toulouse NeuroImaging Center, Centre d'Acquisition et de Traitement des Images, ARAMIS: Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain sain et pathologique, Centre Hospitalier Universitaire de Rouen, Laboratoire d’Imagerie Biomédicale
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,239
Awards: G1258743643, G3103753459, Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime, Predict to prevent frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), G7240651115, Institut de Neurosciences Translationnelles de Paris
OpenAlex ID: W2890455870