Clinical and genetic keys to cerebellar ataxia due to FGF14 GAA expansions.

Diagnosis GAA expansion Hereditary cerebellar ataxia SCA27B

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
26 Dec 2023
Historique:
received: 02 10 2023
revised: 26 11 2023
accepted: 06 12 2023
medline: 28 12 2023
pubmed: 28 12 2023
entrez: 27 12 2023
Statut: aheadofprint

Résumé

SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability. We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor. A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.

Sections du résumé

BACKGROUND BACKGROUND
SCA27B caused by FGF14 intronic heterozygous GAA expansions with at least 250 repeats accounts for 10-60% of cases with unresolved cerebellar ataxia. We aimed to assess the size and frequency of FGF14 expanded alleles in individuals with cerebellar ataxia as compared with controls and to characterize genetic and clinical variability.
METHODS METHODS
We sized this repeat in 1876 individuals from France sampled for research purposes in this cross-sectional study: 845 index cases with cerebellar ataxia and 324 affected relatives, 475 controls, as well as 119 cases with spastic paraplegia, and 113 with familial essential tremor.
FINDINGS RESULTS
A higher frequency of expanded allele carriers in index cases with ataxia was significant only above 300 GAA repeats (10.1%, n = 85) compared with controls (1.1%, n = 5) (p < 0.0001) whereas GAA
INTERPRETATION CONCLUSIONS
SCA27B diagnosis must consider both the phenotype and GAA expansion size. In carriers of GAA
FUNDING BACKGROUND
This work was supported by the Fondation pour la Recherche Médicale, grant number 13338 to JLM, the Association Connaître les Syndrome Cérébelleux - France (to GS) and by the European Union's Horizon 2020 research and innovation program under grant agreement No 779257 ("SOLVE-RD" to GS). DP holds a Fellowship award from the Canadian Institutes of Health Research (CIHR). SK received a grant (01GM1905C) from the Federal Ministry of Education and Research, Germany, through the TreatHSP network. This work was supported by the Australian Government National Health and Medical Research Council grants (GNT2001513 and MRFF2007677) to MB and PJL.

Identifiants

DOI: 10.1016/j.ebiom.2023.104931 PMID: 38150853
pubmed: 38150853
pii: S2352-3964(23)00497-8
doi: 10.1016/j.ebiom.2023.104931
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

104931

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests MA received consulting fees from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen; honoraria from Reata pharmaceuticals, Merz, AbbVie, Orkyn, Ever Pharma, Ipsen and participated on an advisory board for Reata Pharmaceuticals. ILB received grants from Pfizer, Fondation Plan Alzheimer, JPND/ANR, Alector; consulting fees from Prevail Therapeutics, Alector, JEITO and participated on an advisory board of Prevail Therapeutics. CM reveived financial support for attending meetings and travel from Nutricia and participated on an advisory board of Medesis Pharma society. BD had public funding contracts for Clinical Research: Contrat de Recherche Clinique (CRC) 2021 (APHP), CRC 2023 (APHP) and Agence Régionale de Santé (ARS); received honoraria from MERZ, IPSEN Pharma, LVL Medical; received support for attending meetings from MERZ Pharma, ADELIA; participated on an advisory board of MERZ, ORION Pharma and received equipment from MERZ. SF received support for participation in national and international meetings from Alnylam. MB received honoraria for thesis examinations; is member of Australian Academy of Health and Medical Sciences Australian Learned Academies Data Internetworking Network (ALADIN) Project Steering Committee; Australian Academy of Health and Medical Sciences Reports Committee; Clinical Genomics Advisory Committee, Kinghorn Sequencing Center; Gen V Scientific Advisory Committee, Murdoch Children's Research Institute; Viertel Foundation Medical Advisory Board; Australian Academy of Health and Medical Sciences Reports Committee; Present American Epilepsy Society Basic Sciences Committee; Gen V Bioresource Genetics Working Group. AD received grants from Biogen, WAVELIFE, ROCHE, TRIPLET Therapeutics, NIH RO1 (National Institute of Health), National Hospital Clinical Research Program; consulting fees from Wavelife science, ROCHE, TRIPLET Therapeutics, Pfizer, ASKBIO, Genome Quebec, VICO therapeutics; participated on an advisory board for REATA; is the president of the Société Francophone de Neurogénétique.

Auteurs

Jean-Loup Méreaux (JL)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Claire-Sophie Davoine (CS)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

David Pellerin (D)

Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC, Canada; Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology and the National Hospital for Neurology and Neurosurgery, University College London, London, United Kingdom.

Giulia Coarelli (G)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Unité de Génétique Clinique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Marie Coutelier (M)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Claire Ewenczyk (C)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Unité de Génétique Clinique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Marie-Lorraine Monin (ML)

Centre de Reference Maladies Rares « Neurogénétique », Service de Génétique Médicale, Bordeaux University Hospital (CHU Bordeaux), 33000, Bordeaux, France.

Mathieu Anheim (M)

Department of Neurology, Strasbourg University Hospital, 67098, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), INSERM-U964, CNRS-UMR7104, University of Strasbourg, 67400, Illkirch-Graffenstaden, France.

Isabelle Le Ber (I)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Stéphane Thobois (S)

Department of Neurology C, Expert Parkinson Centre NS-Park/F-CRIN, Hospices Civils de Lyon, Pierre Wertheimer Neurological Hospital, 69677, Bron, France; Marc Jeannerod Cognitive Neuroscience Institute, CNRS, UMR 5229, Bron, France; Faculté de Médecine Et de Maïeutique Lyon Sud Charles Mérieux, Université Claude Bernard Lyon 1, Université de Lyon, Lyon, France.

Florent Gobert (F)

Neuro-Intensive Care Unit, Hospices Civils de Lyon, Neurological Hospital Pierre-Wertheimer, Lyon, France; University Lyon I, Villeurbanne, France.

Léna Guillot-Noël (L)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Sylvie Forlani (S)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Ludmila Jornea (L)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Anna Heinzmann (A)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Aude Sangare (A)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Department of Neurophysiology, University Hospital Group APHP-Sorbonne University, Pitié-Salpêtrière Site, Paris, France.

Bertrand Gaymard (B)

Department of Neurophysiology, University Hospital Group APHP-Sorbonne University, Pitié-Salpêtrière Site, Paris, France.

Lucie Guyant-Maréchal (L)

Neurophysiology Department, Rouen University Hospital, Rouen, France; Medical Genetics Department, Rouen University Hospital, Rouen, France.

Perrine Charles (P)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Unité de Génétique Clinique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Cecilia Marelli (C)

MMDN, University Montpellier, EPHE, INSERM and Expert Center for Neurogenetic Diseases, CHU, 34095, Montpellier, France.

Jérôme Honnorat (J)

Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, MeLiS Institute UMR CNRS 5284 - INSERM U1314, Université Claude Bernard Lyon 1, Lyon, France.

Bertrand Degos (B)

Neurology Department, Avicenne Hospital, APHP, Hôpitaux Universitaires de Paris-Seine Saint Denis (HUPSSD), Sorbonne Paris Nord, Réseau NS-PARK/FCRIN, Bobigny, France.

François Tison (F)

Institut des Maladies Neurodégénératives-Clinique (IMNc), University Hospital Bordeaux, Bordeaux, France; Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux University, Bordeaux, France.

Sophie Sangla (S)

Neurology Department, Hôpital Fondation Adolphe de Rothschild, Paris, France.

Marion Simonetta-Moreau (M)

Department of Neurology, University Hospital of Toulouse, 31300, Toulouse, France; Toulouse NeuroImaging Center (ToNIC), Inserm, UPS, Université de Toulouse, 31024, Toulouse, France; Clinical Investigation Center (CIC 1436), Toulouse University Hospital, INSERM, 31059, Toulouse, France.

François Salachas (F)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Département de Neurologie, Assistance Publique Hôpitaux de Paris (APHP), Centre de Référence SLA Ile de France, Hôpital de la Pitié-Salpêtrière, Paris, France.

Maya Tchikviladzé (M)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Giovanni Castelnovo (G)

Department of Neurology, Nîmes University Hospital, Hopital Caremeau, Nîmes, France.

Fanny Mochel (F)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Stephan Klebe (S)

Department of Neurology, University Hospital Essen, Essen, Germany.

Anna Castrioto (A)

Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Neurology Department, 38000, Grenoble, France.

Silvia Fenu (S)

Unit of Rare Neurological Diseases, Department of Clinical Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.

Aurélie Méneret (A)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Département de Neurologie, Hôpital de la Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris (APHP), Paris, France.

Frédéric Bourdain (F)

Service de Neurologie, Centre Hospitalier de la Côte Basque, Bayonne, France.

Marion Wandzel (M)

Laboratoire de Génétique Médicale, CHRU Nancy, Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France.

Virginie Roth (V)

Laboratoire de Génétique Médicale, CHRU Nancy, Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France.

Céline Bonnet (C)

Laboratoire de Génétique Médicale, CHRU Nancy, Université de Lorraine, INSERM UMR_S1256, NGERE, Nancy, France.

Florence Riant (F)

Service de Génétique Moléculaire Neurovasculaire, AP-HP, Saint Louis Hospital, Paris, France.

Giovanni Stevanin (G)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Bordeaux University (Université de Bordeaux), Equipe « Neurogénétique Translationnelle - NRGEN », INCIA CNRS UMR5287, EPHE, 33000, Bordeaux, France.

Sandrine Noël (S)

Unité de Neurogénétique Moléculaire et Cellulaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Anne-Laure Fauret-Amsellem (AL)

Unité de Neurogénétique Moléculaire et Cellulaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.

Melanie Bahlo (M)

Population Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Department of Medical Biology, University of Melbourne, Parkville, VIC, 3052, Australia.

Paul J Lockhart (PJ)

Bruce Lefroy Centre, Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Parkville, VIC, 3052, Australia.

Bernard Brais (B)

Department of Neurology and Neurosurgery, Montreal Neurological Hospital and Institute, McGill University, Montreal, QC, Canada.

Mathilde Renaud (M)

Service de Génétique Clinique et de Neurologie, Hôpital Brabois, Nancy, France; INSERM Unité 1256 N-GERE (Nutrition-Genetics and Environmental Risk Exposure), Université de Lorraine, Nancy, France.

Alexis Brice (A)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France.

Alexandra Durr (A)

Sorbonne Université, Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Paris, France; Unité de Génétique Clinique, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France. Electronic address: alexandra.durr@icm-institute.org.

Classifications MeSH