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Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers

2018; Elsevier BV; Volume: 74; Linguagem: Inglês

10.1016/j.neurobiolaging.2018.09.010

1558-1497

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 Jornéa, Eric Leguern, Alexis Brice, Isabelle Le Ber, 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 Lévy, Bernard‐François Michel, Florence Pasquier, Catherine Thomas-Antérion, Jérémie Pariente, François Sellal, Martine Vercelletto, Eve Benchetrit, Hugo Bertin, Anne Bertrand, Anne Bissery, Stéphanie Bombois, Marie-Paule Boncœur, 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 Lévy, Kelly Martineau, Marie‐Anne Mackowiak, Jacques Monteil, Florence Pasquier, G. Petyt, Pierre-François Pradat, Assi-Hervé Oya, Daisy Rinaldi, Adeline Rollin‐Sillaire, François Salachas, Sabrina Sayah, David Wallon,

Prion Diseases and Protein Misfolding

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.