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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.

Authors
  • Fournier, Clémence1
  • Barbier, Mathieu2
  • Camuzat, Agnès3
  • Anquetil, Vincent1
  • Lattante, Serena4
  • Clot, Fabienne5
  • Cazeneuve, Cécile5
  • Rinaldi, Daisy6
  • Couratier, Philippe7
  • Deramecourt, Vincent8
  • Sabatelli, Mario9
  • Belliard, Serge10
  • Vercelletto, Martine11
  • Forlani, Sylvie12
  • Jornea, Ludmila12
  • Leguern, Eric13
  • Brice, Alexis1
  • Le Ber, Isabelle14
  • 1 Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France. , (France)
  • 2 Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France. Electronic address: [email protected] , (France)
  • 3 Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France; Ecole Pratique des Hautes Etudes - EPHE, PSL research University, Paris, France. , (France)
  • 4 Fondazione Policlinico Universitario A.Gemelli IRCCS, Roma, Università Cattolica del Sacro Cuore, Institute of Genomic Medicine, Roma, Italy. , (Italy)
  • 5 Unité Fonctionnelle de Neurogénétique Moléculaire et Cellulaire, Département de Génétique, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, F-75013 Paris, France. , (France)
  • 6 Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France; National Reference Center for Rare or Early Dementias, Institute of Memory and Alzheimer's Disease IM2A, Department of Neurology, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France. , (France)
  • 7 Centre SLA, CHU de Limoges, Limoges, France. , (France)
  • 8 Univ. Lille, Inserm, CHU Lille, U1172 - Alzheimer and Tauopathies, LabEx DISTALZ, Lille, France. , (France)
  • 9 Fondazione Policlinico Universitario A.Gemelli IRCCS, Roma, Università Cattolica del Sacro Cuore, Department of Geriatrics, Neurosciences and Orthopedics, Clinic Center NEMO-Roma, Roma, Italy. , (Italy)
  • 10 CMRR Bretagne, CHU Rennes, Rennes, France. , (France)
  • 11 CHU Nantes, Centre Mémoire Ressource et Recherche, Département de Neurologie, Université de Nantes, France; INSERM CIC 04, Université de Nantes, Nantes, France. , (France)
  • 12 Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France. , (France)
  • 13 Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Unité Fonctionnelle de Neurogénétique Moléculaire et Cellulaire, Département de Génétique, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière-Charles Foix, F-75013 Paris, France. , (France)
  • 14 Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, Inserm U1127, CNRS UMR 7225, Institut du Cerveau et la Moelle épinière ICM, Hôpital Pitié-Salpêtrière, Paris, France; National Reference Center for Rare or Early Dementias, Institute of Memory and Alzheimer's Disease IM2A, Department of Neurology, AP-HP - Hôpital Pitié-Salpêtrière, Paris, France. Electronic address: [email protected] , (France)
Type
Published Article
Journal
Neurobiology of aging
Publication Date
Sep 19, 2018
Identifiers
DOI: 10.1016/j.neurobiolaging.2018.09.010
PMID: 30337192
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

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