Assessment of Mendelian and risk-factor genes in Alzheimer disease: A prospective nationwide clinical utility study and recommendations for genetic screening.

Autor:	Nicolas G; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France. Electronic address: gaelnicolas@hotmail.com., Zaréa A; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France., Lacour M; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France., Quenez O; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France., Rousseau S; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France., Richard AC; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France., Bonnevalle A; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France., Schramm C; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Genetics and CNRMAJ, F-76000 Rouen, France., Olaso R; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France., Sandron F; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France., Boland A; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France., Deleuze JF; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), Evry, France., Andriuta D; Service de Neurologie CHU Amiens et Laboratoire de Neurosciences Fonctionnelles et Pathologies, Université de Picardie Jules Verne, Amiens, France., Anthony P; Department of Neurology, Hôpitaux Civils de Colmar, F-68000 Colmar, France., Auriacombe S; Univ. Bordeaux, CNRS UMR 5293, Institut des Maladies Neurodégénératives, Bordeaux, France., Balageas AC; Centre Mémoire Ressources et Recherche, CHRU de Tours, Tours, France., Ballan G; Centre Hospitalier de la Côte Basque, Bayonne, France., Barbay M; Service de Neurologie CHU Amiens et Laboratoire de Neurosciences Fonctionnelles et Pathologies, Université de Picardie Jules Verne, Amiens, France., Béjot Y; Department of Neurology, University Hospital of Dijon, University of Burgundy, Dijon, France., Belliard S; Unité de recherche 1077 INSERM-EPHE-UNICAEN Neuropsychologie & Imagerie de la Mémoire Humaine (NIMH), Caen, France; Centre Mémoire Ressources et Recherche Haute Bretagne, CHU Rennes, Rennes, France., Benaiteau M; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Bennys K; Memory Ressources Research Center, Department of Neurology, University Hospital of Montpellier, Montpellier, France., Bombois S; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Boutoleau-Bretonnière C; CHU Nantes, Memory Center, Inserm CIC4, 44093 Nantes, France., Branger P; Department of Neurology, Caen University Hospital, Caen, France., Carlier J; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Cartz-Piver L; Memory Ressources Research Center, Department of Neurology, University Hospital of Limoges, France Inserm U1094, IRD U270, EPIMACT, Université of Limoges, Limoges, France., Cassagnaud P; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Ceccaldi MP; Institute of Neurophysiopathology UMR 7051 Aix Marseille Université & Assistance Publique de Marseille, Marseille, France., Chauviré V; CMRR, CRMR Neurogénétique, Service de Neurologie, CHU d'ANGERS, Angers, France., Chen Y; Univ Lille, CHU Lille, Inserm 1172, Memory center, CNRMAJ, LiCEND, Labex DistAlz 59000 Lille, France., Cogez J; Department of Neurology, Caen University Hospital, Caen, France., Cognat E; Cognitive Neurology Center, AP-HP.Nord, Site Lariboisière Fernand-Widal, Paris, France; Université Paris Cité, UMR-S 1144, INSERM, Paris, France., Contegal-Callier F; Hospices Civils de Beaune, Consultation mémoire, Beaune, France., Corneille L; Institute of Neurophysiopathology UMR 7051 Aix Marseille Université & Assistance Publique de Marseille, Marseille, France., Couratier P; CMRR Limoges, Service de Neurologie CHU Limoges, Limoges, France., Cretin B; CMRR d'Alsace, Service de Neurologie, CHU Strasbourg, Strasbourg, France., Crinquette C; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Dauriat B; Service de Génétique Médicale, Hopital Mère-Enfant, CHU Limoges, Limoges, France., Dautricourt S; CMRR Lyon, Department of Neurology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France., de la Sayette V; Department of Neurology, Caen University Hospital, Caen, France; Normandie UNIV, UNICAEN, PSL Research University, EPHE, INSERM, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France., de Liège A; Service de Neurologie, APHP, Hôpital Avicenne, Université Sorbonne Paris Nord, Bobigny, France., Deffond D; CMRR Clermont-Ferrand, Service de Neurologie, CHU Clermont-Ferrand, Clermont-Ferrand, France., Demurger F; Service de génétique, CHBA, Vannes, France., Deramecourt V; Univ Lille, CHU Lille, Inserm 1172, Memory center, CNRMAJ, LiCEND, Labex DistAlz 59000 Lille, France., Derollez C; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Dionet E; CMRR Clermont-Ferrand, Service de Neurologie, CHU Clermont-Ferrand, Clermont-Ferrand, France., Doco Fenzy M; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France; CHU Nantes, Service de Génétique, Nantes, France; CHU Reims, Service de Génétique, Reims, France., Dumurgier J; Cognitive Neurology Center, AP-HP.Nord, Site Lariboisière Fernand-Widal, Paris, France; Université Paris Cité, UMR-S 1144, INSERM, Paris, France., Dutray A; Service de Neurologie, Centre Hospitalier Perpignan, Perpignan, France., Etcharry-Bouyx F; CMRR, CRMR Neurogénétique, Service de Neurologie, CHU d'ANGERS, Angers, France., Formaglio M; CMRR Lyon, Department of Neurology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France., Gabelle A; Memory Ressources Research Center, Department of Neurology, University Hospital of Montpellier, Montpellier, France., Gainche-Salmon A; Centre Mémoire Ressources et Recherche Haute Bretagne, CHU Rennes, Rennes, France., Godefroy O; Service de Neurologie CHU Amiens et Laboratoire de Neurosciences Fonctionnelles et Pathologies, Université de Picardie Jules Verne, Amiens, France., Graber M; Centre mémoire ressources et recherche, CHU Dijon, Dijon, France., Gregoire C; CHU de Bordeaux, Pôle de Neurosciences Cliniques, Centre Mémoire de Ressources et de Recherche, Bordeaux, France., Grimaldi S; Institute of Neurophysiopathology UMR 7051 Aix Marseille Université & Assistance Publique de Marseille, Marseille, France., Gueniat J; Centre mémoire ressources et recherche, CHU Dijon, Dijon, France., Gueriot C; Institute of Neurophysiopathology UMR 7051 Aix Marseille Université & Assistance Publique de Marseille, Marseille, France., Guillet-Pichon V; CMRR, CRMR Neurogénétique, Service de Neurologie, CHU d'ANGERS, Angers, France., Haffen S; Centre mémoire Recherche Ressources, Service de Neurologie, CHU Besançon, Besançon, France., Hanta CR; Centre Mémoire Ressources et Recherche Haute Bretagne, CHU Rennes, Rennes, France., Hardy C; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France., Hautecloque G; Department of Neurology, Hôpitaux Civils de Colmar, F-68000 Colmar, France., Heitz C; Institut du cerveau Trocadero, Paris, France; Neurology Department, Hôpital Universitaire de Nîmes, Nîmes, France., Hourregue C; Cognitive Neurology Center, AP-HP.Nord, Site Lariboisière Fernand-Widal, Paris, France., Jonveaux T; Centre Mémoire de Ressources et de Recherche de Lorraine Service de Neurologie CHRU Nancy, Nancy, France; Laboratoire 2LPN EA 7489 Université de Lorraine, Nancy, France., Jurici S; Consultation Mémoire, Service de Gériatrie, Centre Hospitalier Perpignan, Perpignan, France., Koric L; Institute of Neurophysiopathology UMR 7051 Aix Marseille Université & Assistance Publique de Marseille, Marseille, France; Aix-Marseille Univ, UMR 7249, CNRS, Centrale Marseille, Institut Fresnel, Marseille, France., Krolak-Salmon P; CMRR Lyon, Department of Neurology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France., Lagarde J; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France; Université Paris-Cité, F-75006 Paris, France; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, F-91401, Orsay, France., Lanoiselée HM; Service de neurologie, Centre Hospitalier Régional d'Orléans, Orléans, France., Laurens B; CHU de Bordeaux, Pôle de Neurosciences Cliniques, Centre Mémoire de Ressources et de Recherche, Bordeaux, France., Le Ber I; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Le Guyader G; Service de Génétique, CHU Poitiers, 86022 Poitiers Cedex, France., Leblanc A; Consultations neurologiques, HIA Clermont-Tonnerre, Brest, France; Service de neurologie, CHU Cavale-Blanche, Brest, France., Lebouvier T; Univ Lille, CHU Lille, Inserm 1172, Memory center, CNRMAJ, LiCEND, Labex DistAlz 59000 Lille, France., Levy R; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Lippi A; Service de Neurologie, Hopital Gui de Chauliac, CHU de Montpellier, Montpellier, France., Mackowiak MA; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Magnin E; Laboratoire de neuroscience, Université de Franche-Comté UFC et Service de Neurologie, CMRR, CHU Besançon, Besançon, France., Marelli C; Service de Neurologie, Hopital Gui de Chauliac, CHU de Montpellier, Montpellier, France., Martinaud O; Department of Neurology, Caen University Hospital, Caen, France; Normandie UNIV, UNICAEN, PSL Research University, EPHE, INSERM, CHU de Caen, Neuropsychologie et Imagerie de la Mémoire Humaine, Caen, France., Maureille A; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Migliaccio R; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Milongo-Rigal E; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Mohr S; Centre mémoire ressources et recherche, CHU Dijon, Dijon, France., Mollion H; CMRR Lyon, Department of Neurology, University Hospital of Lyon, Hospices Civils de Lyon, Lyon, France., Morin A; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France; Département de Psychiatrie, Centre Hospitalier du Rouvray, Université de Rouen, 76000, Sotteville-lès-Rouen, France., Nivelle J; CH Ales Cévennes, Alès, France., Noiray C; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France; Université Paris-Cité, F-75006 Paris, France; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, F-91401, Orsay, France., Olivieri P; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France; Université Paris-Cité, F-75006 Paris, France; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, F-91401, Orsay, France., Paquet C; Cognitive Neurology Center, AP-HP.Nord, Site Lariboisière Fernand-Widal, Paris, France; Université Paris Cité, UMR-S 1144, INSERM, Paris, France., Pariente J; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Toulouse NeuroImaging Center (ToNIC), INSERM-University of Toulouse Paul Sabatier, Toulouse, France., Pasquier F; Univ Lille, CHU Lille, Inserm 1172, Memory center, CNRMAJ, LiCEND, Labex DistAlz 59000 Lille, France., Perron A; Department of Neurology, Hôpitaux Civils de Colmar, F-68000 Colmar, France., Philippi N; CMRR d'Alsace, Service de Neurologie, CHU Strasbourg, Strasbourg, France., Planche V; Univ. Bordeaux, CNRS UMR 5293, Institut des Maladies Neurodégénératives, Bordeaux, France; CHU de Bordeaux, Pôle de Neurosciences Cliniques, Centre Mémoire de Ressources et de Recherche, Bordeaux, France., Pouclet-Courtemanche H; Department of Neurology, CHU Nantes, Nantes, France., Rafiq M; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France; Toulouse NeuroImaging Center (ToNIC), INSERM-University of Toulouse Paul Sabatier, Toulouse, France., Rollin-Sillaire A; CHU Lille, Memory Center, CNRMAJ 59000 Lille, France., Roué-Jagot C; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France; Université Paris-Cité, F-75006 Paris, France; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, F-91401, Orsay, France., Saracino D; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Sarazin M; Department of Neurology of Memory and Language, GHU Paris Psychiatrie & Neurosciences, Hôpital Sainte Anne, F-75014, Paris, France; Université Paris-Cité, F-75006 Paris, France; Université Paris-Saclay, BioMaps, Service Hospitalier Frédéric Joliot CEA, CNRS, Inserm, F-91401, Orsay, France., Sauvée M; Centre Mémoire de Ressources et de Recherche, Pôle PReNeLe, CHU Grenoble Alpes CS 10226, 38043 Grenoble Cedex 9, France; Unité de recherche mixte Université Grenoble Alpes/Université Savoie Montblanc, CNRS UMR 5115, Laboratoire de Psychologie et Neurocognition (LPNC), 38000 Grenoble, France., Sellal F; Department of Neurology, Hôpitaux Civils de Colmar, F-68000 Colmar, France; University of Strasbourg, Medicine Faculty, INSERM, U-1118, Strasbourg, France., Teichmann M; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Thauvin C; Genetics Center, University Hospital of Dijon, University of Burgundy, Dijon, France., Thomas Q; Department of Neurology, University Hospital of Dijon, University of Burgundy, Dijon, France; Genetics Center, University Hospital of Dijon, University of Burgundy, Dijon, France., Tisserand C; Neurology Department, Hôpital Pierre-Paul Riquet, Centre Hospitalier Universitaire de Toulouse, Toulouse, France., Turpinat C; Service de Neurologie, Hopital Gui de Chauliac, CHU de Montpellier, Montpellier, France., Van Damme L; Service de Neurologie, Centre Hospitalier Perpignan, Perpignan, France., Vercruysse O; Department of Neurology, Saint Brieuc Hospital, Saint-Brieuc, France., Villain N; Sorbonne Université, INSERM U1127, CNRS 7235, Institut du Cerveau - ICM, Paris, France; AP-HP Sorbonne Université, Pitié-Salpêtrière Hospital, Department of Neurology, Institute of Memory and Alzheimer's Disease, Paris, France., Wagemann N; CHU Nantes, Memory Center, Inserm CIC4, 44093 Nantes, France., Charbonnier C; Univ Rouen Normandie, Inserm U1245 and CHU Rouen, Department of Biostatistics and CNRMAJ, F-76000 Rouen, France., Wallon D; Univ Rouen Normandie, Normandie Univ, Inserm U1245 and CHU Rouen, Department of Neurology and CNRMAJ, F-76000 Rouen, France.
Jazyk:	angličtina
Zdroj:	Genetics in medicine : official journal of the American College of Medical Genetics [Genet Med] 2024 May; Vol. 26 (5), pp. 101082. Date of Electronic Publication: 2024 Jan 24.
DOI:	10.1016/j.gim.2024.101082
Abstrakt:	Purpose: To assess the likely pathogenic/pathogenic (LP/P) variants rates in Mendelian dementia genes and the moderate-to-strong risk factors rates in patients with Alzheimer disease (AD). Methods: We included 700 patients in a prospective study and performed exome sequencing. A panel of 28 Mendelian and 6 risk-factor genes was interpreted and returned to patients. We built a framework for risk variant interpretation and risk gradation and assessed the detection rates among early-onset AD (EOAD, age of onset (AOO) ≤65 years, n = 608) depending on AOO and pedigree structure and late-onset AD (66 < AOO < 75, n = 92). Results: Twenty-one patients carried a LP/P variant in a Mendelian gene (all with EOAD, 3.4%), 20 of 21 affected APP, PSEN1, or PSEN2. LP/P variant detection rates in EOAD ranged from 1.7% to 11.6% based on AOO and pedigree structure. Risk factors were found in 69.5% of the remaining 679 patients, including 83 (12.2%) being heterozygotes for rare risk variants, in decreasing order of frequency, in TREM2, ABCA7, ATP8B4, SORL1, and ABCA1, including 5 heterozygotes for multiple rare risk variants, suggesting non-monogenic inheritance, even in some autosomal-dominant-like pedigrees. Conclusion: We suggest that genetic screening should be proposed to all EOAD patients and should no longer be prioritized based on pedigree structure. Competing Interests: Conflict of Interest The authors have no conflict of interest to declare. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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