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

Clémence Fournier 1 Mathieu Barbier 1 Agnès Camuzat 1, 2 Vincent Anquetil 3, 1 Serena Lattante 4 Fabienne Clot 3 Cécile Cazeneuve 5 Mario Sabatelli 4 Sylvie Forlani 1 Ludmila Jornea 1 Eric Leguern 3, 1 Alexis Brice 1 Sophie Auriacombe 6 Serge Belliard 7 Frédéric Blanc 8 Claire Bouteleau-Bretonnière 9 Mathieu Ceccaldi 10 Mira Didic 10 Charles Duyckaerts 1 Frédérique Etcharry-Bouix 11 Véronique Golfier 7 Lucette Lacomblez 1 Bernard-François Michel 12 Catherine Thomas-Antérion 13 Jérémie Pariente 14 François Sellal 15 Martine Vercelletto 16 Eve Benchetrit 17 Hugo Bertin 18 Anne Bertrand 3 Anne Bissery 3 Stéphanie Bombois 19 Marie-Paule Boncoeur 20, 21 Pascaline Cassagnaud 19 Mathieu Chastan 22 Yaohua Chen 19 Marie Chupin 18 Olivier Colliot 23 Philippe Couratier 20, 24 Xavier Delbeucq 19 Vincent Deramecourt 19 Christine Delmaire 25 Emmanuel Gérardin 26 Claude Hossein-Foucher 27 Bruno Dubois 1 Marie Habert 1 Didier Hannequin 28 Géraldine Lautrette 24 Thibaud Lebouvier 29 Isabelle Le Ber 1 Stéphane Lehéricy 1 Benjamin Le Toullec 30 Richard Lévy 3 Martine Martineau 1 Anne Mackowiak 19 Jacques Monteil 31 Florence Pasquier 19 Grégory Petyt 19 François Pradat 3 Assi-Hervé Oya 3 Daisy Rinaldi 1 Adeline Rollin-Sillaire 32 François Salachas 3 Sabrina Sayah 1 David Wallon 28
23 ARAMIS - Algorithms, models and methods for images and signals of the human brain
SU - Sorbonne Université, Inria de Paris, ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute
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.
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Contributeur : Elisabeth Grelier <>
Soumis le : mercredi 20 février 2019 - 09:15:58
Dernière modification le : lundi 4 novembre 2019 - 17:52:07

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Clémence Fournier, Mathieu Barbier, Agnès Camuzat, Vincent Anquetil, Serena Lattante, et al.. Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers. Neurobiology of Aging, Elsevier, 2019, 74, pp.234.e1-234.e8. ⟨10.1016/j.neurobiolaging.2018.09.010⟩. ⟨hal-02025976⟩

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