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; Mario Sabatelli; Sylvie Forlani; Ludmila Jornea; Eric Leguern; Alexis Brice; Sophie Auriacombe; Serge Belliard; 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; 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 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; Daisy Rinaldi; Adeline Rollin-Sillaire; François Salachas; Sabrina Sayah; David Wallon

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

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 [APHP]

4 Unicatt - Università Cattolica del Sacro Cuore [Roma]

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

6 Service de neurologie [Bordeaux]

7 CHU Pontchaillou [Rennes]

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

9 CHU Nantes - Centre hospitalier universitaire de Nantes

10 APHM - Assistance Publique - Hôpitaux de Marseille

11 CHU Angers - Centre Hospitalier Universitaire d'Angers

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

13 CMRR - Centre de Mémoire de Ressource et Recherche

14 Imagerie cérébrale et handicaps neurologiques

15 Service de Neurologie [Strasbourg]

16 Service de neurologie [Nantes]

17 Service de neurologie 1 [CHU Pitié-Salpétrière]

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

19 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]

20 NET - Neuroépidémiologie Tropicale

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 Service de Neurologie [CHU Limoges]

25 Services de neuroradiologie [Lille]

26 CHU Rouen

27 Troubles cognitifs vasculaires et dégénératifs

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

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

30 CIC Pitié Neurosciences

31 CHU Limoges

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

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 : Elisabeth Grelier <>
Soumis le : mercredi 20 février 2019 - 09:15:58
Dernière modification le : vendredi 11 octobre 2019 - 20:22:46

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

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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

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