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

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; Eric Leguern; Alexis Brice; Sophie Auriacombe; Frédéric Blanc; Claire Bouteleau-Bretonnière; Mathieu Ceccaldi; Mira Didic; Charles Duyckaerts; Frédérique Etcharry-Bouix; Véronique Golfier; Lucette Lacomblez; Bernard-François Michel; Catherine Thomas-Antérion; Jérémie Pariente; François Sellal; Eve Benchetrit; Hugo Bertin; Anne Bertrand; Anne Bissery; Stéphanie Bombois; Marie-Paule Boncoeur; Pascaline Cassagnaud; Mathieu Chastan; Yaohua Chen; Marie Chupin; Olivier Colliot; Xavier Delbeucq; Christine Delmaire; Emmanuel Gérardin; Claude Hossein-Foucher; Bruno Dubois; Marie Habert; Didier Hannequin; Géraldine Lautrette; Thibaud Lebouvier; Isabelle Le Ber; Stéphane Lehéricy; Benjamin Le Toullec; Richard Lévy; Martine Martineau; Anne Mackowiak; Jacques Monteil; Florence Pasquier; Grégory Petyt; François Pradat; Assi-Hervé Oya; Adeline Rollin-Sillaire; François Salachas; Sabrina Sayah; David Wallon

doi:10.1016/j.neurobiolaging.2018.09.010

Article dans une revue

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 Daisy Rinaldi ¹ Philippe Couratier ^{6, 7} Vincent Deramecourt ⁸ Mario Sabatelli ⁴ Serge Belliard ⁹ Martine Vercelletto ¹⁰ Sylvie Forlani ¹ Ludmila Jornea ¹ Eric Leguern ^{3, 1} Alexis Brice ¹ Sophie Auriacombe ¹¹ Frédéric Blanc ¹² Claire Bouteleau-Bretonnière ¹³ Mathieu Ceccaldi ¹⁴ Mira Didic ¹⁴ Charles Duyckaerts ¹ Frédérique Etcharry-Bouix ¹⁵ Véronique Golfier ⁹ Lucette Lacomblez ¹ Bernard-François Michel ¹⁶ Catherine Thomas-Antérion ¹² Jérémie Pariente ¹⁷ François Sellal ¹⁸ Eve Benchetrit ¹⁹ Hugo Bertin ²⁰ Anne Bertrand ³ Anne Bissery ³ Stéphanie Bombois ⁸ Marie-Paule Boncoeur ^{6, 21} Pascaline Cassagnaud ⁸ Mathieu Chastan ²² Yaohua Chen ⁸ Marie Chupin ²⁰ Olivier Colliot ²³ Xavier Delbeucq ⁸ Christine Delmaire ²⁴ Emmanuel Gérardin ²⁵ Claude Hossein-Foucher ²⁶ Bruno Dubois ¹ Marie Habert ¹ Didier Hannequin ²⁷ Géraldine Lautrette ⁷ Thibaud Lebouvier ²⁸ Isabelle Le Ber ¹ Stéphane Lehéricy ¹ Benjamin Le Toullec ²⁹ Richard Lévy ³ Martine Martineau ¹ Anne Mackowiak ⁸ Jacques Monteil ³⁰ Florence Pasquier ⁸ Grégory Petyt ⁸ François Pradat ³ Assi-Hervé Oya ³ Adeline Rollin-Sillaire ³¹ François Salachas ³ Sabrina Sayah ¹ David Wallon ²⁷

1 ICM - Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute

2 EPHE - École pratique des hautes études

3 CHU Pitié-Salpêtrière [AP-HP]

4 Unicatt - Università Cattolica del Sacro Cuore [Roma]

5 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]

6 NET - Neuroépidémiologie Tropicale

7 Service de Neurologie [CHU Limoges]

8 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]

9 CHU Pontchaillou [Rennes]

10 Service de neurologie [Nantes]

11 Service de neurologie [Bordeaux]

12 CMRR Strasbourg - Centre Mémoire Ressources et Recherche [Strasbourg]

13 CHU Nantes - Centre hospitalier universitaire de Nantes

14 APHM - Assistance Publique - Hôpitaux de Marseille

15 CHU Angers - Centre Hospitalier Universitaire d'Angers

16 Hôpitaux Sud - Hôpital Sainte-Marguerite [CHU - APHM]

17 ToNIC - Toulouse Neuro Imaging Center

18 Service de Neurologie [Strasbourg]

19 Service de neurologie 1 [CHU Pitié-Salpétrière]

20 Centre d'Acquisition et de Traitement des Images [Paris]

21 Service de Radiologie et Imagerie Médicale [CHU Limoges]

22 Service de médecine nucléaire [Rouen]

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

24 Services de neuroradiologie [Lille]

25 CHU Rouen

26 Troubles cognitifs vasculaires et dégénératifs

27 Centre Normandie de Génomique et de Médecine Personnalisée - Département de génétique [CHU Rouen]

28 Neuropathies du système nerveux entérique et pathologies digestives; implication des cellules gliales entériques

29 CIC Pitié Neurosciences

30 CHU Limoges

31 Département de neurologie[Lille]

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.

Keywords : Amyotrophic Lateral sclerosis Anticipation TDP-43 Frontotemporal lobar degeneration Frontotemporal dementia C9orf72

Type de document :

Article dans une revue

Domaine :

Sciences du Vivant [q-bio] / Santé publique et épidémiologie

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https://hal-unilim.archives-ouvertes.fr/hal-02025976
Contributeur : Laurent Jonchère <>
Soumis le : lundi 12 octobre 2020 - 14:50:06
Dernière modification le : jeudi 10 décembre 2020 - 03:42:58

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