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Tytuł:
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New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.
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Autorzy:
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Alonso-Pérez J; Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
González-Quereda L; U705 CIBERER, Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Spain.
Bello L; Department of Neuroscience, University of Padova, Padova, Italy.
Guglieri M; John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Straub V; John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
Gallano P; U705 CIBERER, Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.; Centro de Investigación Biomédica en Red en Enfermedades Raras (CIBERER), Spain.
Semplicini C; Department of Neuroscience, University of Padova, Padova, Italy.
Pegoraro E; Department of Neuroscience, University of Padova, Padova, Italy.
Zangaro V; Department of Neuroscience, University of Padova, Padova, Italy.
Nascimento A; Neuromuscular Disorder Unit, Hospital Sant Joan de Deu, Barcelona, Spain.
Ortez C; Neuromuscular Disorder Unit, Hospital Sant Joan de Deu, Barcelona, Spain.
Comi GP; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Dino Ferrari Centre, University of Milan, Milan, Italy.
Dam LT; Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
De Visser M; Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
van der Kooi AJ; Department of Neurology, Amsterdam UMC, University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Garrido C; Neuropediatric Department, Centro Hospitalar do Porto, Porto, Portugal.
Santos M; Neuropediatric Department, Centro Hospitalar do Porto, Porto, Portugal.
Schara U; Neuromuscular Centre for Children and Adolescents, Department of Paediatric Neurology, University Hospital Essen, Essen, Germany.
Gangfuß A; Neuromuscular Centre for Children and Adolescents, Department of Paediatric Neurology, University Hospital Essen, Essen, Germany.
Løkken N; Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Storgaard JH; Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Vissing J; Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Schoser B; Friedrich-Baur-Institute, Department of Neurology Klinikum München Ludwig-Maximilians-University Munich, Munich, Germany.
Dekomien G; Department of Human Genetics, Ruhr-University Bochum, Germany.
Udd B; Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland.
Palmio J; Neuromuscular Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland.
D'Amico A; Unit of Neuromuscular and Neurodegenerative Diseases, Department of Neurosciences, Bambino Gesù Children's Hospital, Rome, Italy.
Politano L; Cardiomiology and Medical Genetics, Department of Experimental Medicine, University of Campania, Naples, Italy.
Nigro V; Department of Precision Medicine - University of Campania, Naples, Italy.
Bruno C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Panicucci C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Sarkozy A; Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, UK.
Abdel-Mannan O; Dubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, UCL Great Ormond Street Institute of Child Health, London, UK.
Alonso-Jimenez A; Neuromuscular Reference Center, Department of Neurology, Antwerp University Hospital, Antwerp, Belgium.
Claeys KG; Department of Neurology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.; Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven, Leuven, Belgium.
Gomez-Andrés D; Paediatric Neuromuscular disorders Unit, Pediatric Neurology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Munell F; Paediatric Neuromuscular disorders Unit, Pediatric Neurology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Costa-Comellas L; Paediatric Neuromuscular disorders Unit, Pediatric Neurology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Research (VHIR), Barcelona, Spain.
Haberlová J; Department of Child Neurology, Charles University, 2nd Medical School, University Hospital Motol, Prague, Czech Republic.
Rohlenová M; Department of Child Neurology, Charles University, 2nd Medical School, University Hospital Motol, Prague, Czech Republic.
Elke V; Department of Neurology, Ghent University and University Hospital Ghent, Ghent, Belgium.
De Bleecker JL; Department of Neurology, Ghent University and University Hospital Ghent, Ghent, Belgium.
Dominguez-González C; Department of Neuroscience, University of Padova, Padova, Italy.; Neuromuscular Unit, Department of Neurology, Hospital Universitario 12 de Octubre, Instituto de Investigación imas12, Madrid, Spain.
Tasca G; UOC Neurologia, Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.
Weiss C; Department of Neuropediatrics, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Deconinck N; Department of Neurology, Queen Fabiola Children's University Hospital (HUDERF), Free University of Brussels, Brussels, Belgium.
Fernández-Torrón R; Neurosciences, BioDonostia Health Research Institute, Hospital Donostia, San Sebastián, Spain.
López de Munain A; Neurosciences, BioDonostia Health Research Institute, Hospital Donostia, San Sebastián, Spain.
Camacho-Salas A; Division of Child Neurology, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain.
Melegh B; Department of Medical Genetics, and Szentagothai Research Center, University of Pécs, School of Medicine, Pécs, Hungary.
Hadzsiev K; Department of Medical Genetics, and Szentagothai Research Center, University of Pécs, School of Medicine, Pécs, Hungary.
Leonardis L; Institute of Clinical Neurophysiology, University Medical Centre, Department of Neurology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Koritnik B; Institute of Clinical Neurophysiology, University Medical Centre, Department of Neurology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Garibaldi M; Neuromuscular and Rare Disease Center, Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), SAPIENZA Università di Roma, Rome, Italy.
de Leon-Hernández JC; Department of Neurology, Hospital Universitario Nuestra Señora de la Candelaria, Tenerife, Spain.
Malfatti E; Department of Neurology, Raymond-Poincaré teaching hospital, centre de référence des maladies neuromusculaires Nord/Est/Ile-de-France, AP-HP, Garches, France.
Fraga-Bau A; Department of Neurology, Álvaro Cunqueiro Hospital, Vigo, Spain.
Richard I; Integrare (UMR_S951), Inserm, Généthon, Univ Evry, Université Paris-Saclay, 91002, Evry, France.
Illa I; Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; Department of Neuroscience, University of Padova, Padova, Italy.
Díaz-Manera J; Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.; U705 CIBERER, Genetics Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain.; John Walton Muscular Dystrophy Research Centre, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK.
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Źródło:
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Brain : a journal of neurology [Brain] 2020 Sep 01; Vol. 143 (9), pp. 2696-2708.
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Typ publikacji:
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Journal Article; Multicenter Study; Observational Study; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Oxford University Press
Original Publication: London.
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MeSH Terms:
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Genetic Association Studies*/methods
Sarcoglycanopathies/*epidemiology
Sarcoglycanopathies/*genetics
Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cohort Studies ; Europe/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Muscular Dystrophies, Limb-Girdle/diagnosis ; Muscular Dystrophies, Limb-Girdle/epidemiology ; Muscular Dystrophies, Limb-Girdle/genetics ; Retrospective Studies ; Sarcoglycanopathies/diagnosis ; Young Adult
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Contributed Indexing:
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Keywords: cohort; limb girdle muscular dystrophies; registries; sarcoglycan; treatment
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Entry Date(s):
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Date Created: 20200903 Date Completed: 20210216 Latest Revision: 20221103
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Update Code:
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20240104
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DOI:
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10.1093/brain/awaa228
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PMID:
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32875335
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Sarcoglycanopathies comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. In 2016, several clinicians involved in the diagnosis, management and care of patients with LGMDR3-6 created a European Sarcoglycanopathy Consortium. The aim of the present study was to determine the clinical and genetic spectrum of a large cohort of patients with sarcoglycanopathy in Europe. This was an observational retrospective study. A total of 33 neuromuscular centres from 13 different European countries collected data of the genetically confirmed patients with sarcoglycanopathy followed-up at their centres. Demographic, genetic and clinical data were collected for this study. Data from 439 patients from 13 different countries were collected. Forty-three patients were not included in the analysis because of insufficient clinical information available. A total of 159 patients had a confirmed diagnosis of LGMDR3, 73 of LGMDR4, 157 of LGMDR5 and seven of LGMDR6. Patients with LGMDR3 had a later onset and slower progression of the disease. Cardiac involvement was most frequent in LGMDR4. Sixty per cent of LGMDR3 patients carried one of the following mutations, either in a homozygous or heterozygous state: c.229C>T, c.739G>A or c.850C>T. Similarly, the most common mutations in LMGDR5 patients were c.525delT or c.848G>A. In LGMDR4 patients the most frequent mutation was c.341C>T. We identified onset of symptoms before 10 years of age and residual protein expression lower than 30% as independent risk factors for losing ambulation before 18 years of age, in LGMDR3, LGMDR4 and LGMDR5 patients. This study reports clinical, genetic and protein data of a large European cohort of patients with sarcoglycanopathy. Improving our knowledge about these extremely rare autosomal recessive forms of LGMD was helped by a collaborative effort of neuromuscular centres across Europe. Our study provides important data on the genotype-phenotype correlation that is relevant for the design of natural history studies and upcoming interventional trials in sarcoglycanopathies.
(© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
Erratum in: Brain. 2023 Jan 5;146(1):e9. (PMID: 36327125)
