Natural history of Becker muscular dystrophy: DMD gene mutations predict clinical severity.

Autor:	Gorgoglione D; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Sabbatini D; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy.; Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences, and Public Health, University of Padova, 35131 Padova, Italy., Riguzzi P; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Capece G; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Pane M; Pediatric Neurology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.; Centro Clinico Nemo Pediatrico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy., Servidei S; Neurophysiopathology unit Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.; Dipartimento Universitario di Neuroscienze, Università Cattolica del Sacro Cuore, 00168 Rome, Italy., Briganti M; Neurophysiopathology unit Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.; Fondazione UILDM Lazio Onlus, 00167 Rome, Italy., Sancricca C; Neurophysiopathology unit Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.; Fondazione UILDM Lazio Onlus, 00167 Rome, Italy., Bruschi F; Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy., Ardissone A; Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy., Masson R; Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy., Gallone A; Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy., Maggi L; Neuroimmunology and Neuromuscular Diseases Unit, Fondazione IRCCS Istituto Neurologico 'Carlo Besta', 20133 Milan, Italy., Picillo E; Medical Genetics and Cardiomyology, University of Campania 'Luigi Vanvitelli', 80138 Napoli, Italy., Politano L; Cardiomyology and Medical Genetics, University of Campania 'Luigi Vanvitelli', 80138 Napoli, Italy., Petrosino A; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Vianello S; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Penzo M; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Villa M; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Sframeli M; Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy., Allegra C; Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy., Barp A; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Di Bari A; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Salmin F; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Albamonte E; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Colacicco G; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Panicucci C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Traverso M; Pediatric Neurology and Muscle Disease Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy., Palermo C; Centro Clinico Nemo Pediatrico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy., Lerario A; Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy., Velardo D; Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milano, Italy., D'Angelo MG; Unit of Rare Diseases of the Central and Peripheral Nervous System, Scientific Institute IRCCS Eugenio Medea, 23842 Bosisio Parini, Italy., Berardinelli A; IRCCS Mondino Foundation, 27100 Pavia, Italy., Gardani A; IRCCS Mondino Foundation, 27100 Pavia, Italy., Nicotra R; Child and Adolescence Neurological Unit, National Neurological Institute Casimiro Mondino Foundation, IRCCS, IRCCS Mondino Foundation, 27100 Pavia, Italy.; Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy., Parravicini S; Child and Adolescence Neurological Unit, National Neurological Institute Casimiro Mondino Foundation, IRCCS, IRCCS Mondino Foundation, 27100 Pavia, Italy.; Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy., Siciliano G; Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy., Ricci G; Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy., Torri F; Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy., Gadaleta G; Neuromuscular Unit, Department of Neurosciences RLM, University of Torino, 10126 Turin, Italy., Urbano G; Neuromuscular Unit, Department of Neurosciences RLM, University of Torino, 10126 Turin, Italy., Rolle E; Neuromuscular Unit, Department of Neurosciences RLM, University of Torino, 10126 Turin, Italy., Ricci F; Neuromuscular Unit, Department of Neurosciences RLM, University of Torino, 10126 Turin, Italy., D'Amico A; IRCCS, Unit of Muscular and Neurodegenerative disorders, Bambino Gesù Children's Hospital, 00165 Rome, Italy., Catteruccia M; IRCCS, Unit of Muscular and Neurodegenerative disorders, Bambino Gesù Children's Hospital, 00165 Rome, Italy., Pini A; IRCCS Istituto delle Scienze Neurologiche di Bologna, Neuromuscular Pediatric Unit, 40139 Bologna, Italy., Giannotta M; IRCCS Istituto delle Scienze Neurologiche di Bologna, Neuromuscular Pediatric Unit, 40139 Bologna, Italy., Battini R; Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.; Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy., Marinella G; Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy., Previtali SC; Neuromuscular Repair Unit, Institute of Experimental Neurology (InSpe), Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milan, Italy., Zambon AA; Neuromuscular Repair Unit, Institute of Experimental Neurology (InSpe), Division of Neuroscience, IRCCS Ospedale San Raffaele, 20132 Milan, Italy., Ferlini A; Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy., Fortunato F; Unit of Medical Genetics, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy., Magri F; Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy., Mongini TE; Neuromuscular Unit, Department of Neurosciences RLM, University of Torino, 10126 Turin, Italy., Sansone VA; The NEMO Clinical Center in Milan, Neurorehabilitation Unit, University of Milan, ASST Niguarda Hospital, 20162 Milan, Italy., Bruno C; Center of Translational and Experimental Myology, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.; Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health-DINOGMI, University of Genova, 16132 Genova, Italy., Messina S; Department of Clinical and Experimental Medicine, University of Messina, 98122 Messina, Italy., Nigro V; Medical Genetics and Cardiomyology, University of Campania 'Luigi Vanvitelli', 80138 Napoli, Italy.; Telethon Institute of Genetics and Medicine, 80078, Italy., Moroni I; Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milan, Italy., Mercuri E; Pediatric Neurology, Università Cattolica del Sacro Cuore, 00168 Roma, Italy.; Centro Clinico Nemo Pediatrico, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Roma, Italy., Bello L; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy., Pegoraro E; Department of Neurosciences, Neuromuscular Center, University of Padova, 35128 Padova, Italy.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2024 Nov 05. Date of Electronic Publication: 2024 Nov 05.
DOI:	10.1093/brain/awae358
Abstrakt:	Background: Becker muscular dystrophy (BMD) is an X-linked neuromuscular disease due to mutations in the DMD gene, leading to a deficient and less functional dystrophin mainly in skeletal and cardiac muscle. Understanding the natural history of BMD is crucial for optimizing patient care and developing targeted treatments. Materials and Methods: Retrospective data were collected from 943 patients diagnosed with BMD based on a combination of clinical, biochemical and genetic criteria followed by 17 Italian neuromuscular centers. Patients' demographics, main signs and symptoms at BMD onset, neuropsychiatric comorbidities, age at loss of ambulation (LoA), cardiac left ventricular ejection fraction (LVEF), pulmonary forced vital capacity (FVC), and DMD mutations were collected. Disease milestones were analysed in specific DMD mutational groups. Results: the median age at the last assessment was 26.0 (16.6-41.9) years, with a median age at diagnosis of 7.5 (4.0-14.0) years. In 55% of patients, the diagnosis was prompted by the incidental finding of hyperCKemia. At the last assessment, 13.5% of patients had lost the ability to walk at a median age estimated by Kaplan-Meier analysis of 69 years. Thirty percent of patients exhibited left ventricular impairment and 2.7% respiratory involvement. Ten percent of patients carried out-of-frame mutations, 4% nonsense mutations, and 86% in-frame deletions/duplications. The subset of in-frame deletions was further classified based on the specific mutations. Patients carrying del45-49 compared to del45-47 were associated with an earlier LoA (P=1×10-4), where patients with del45-55 (P=.005), del48 (P=.02), and del48-49 (P=.02) correlated with a later LoA compared to del45-47. del45-55 (P=.002) and del48 (P=.003) were significantly associated with decreased odds of developing a pathological LVEF% compared to del45-47. Conclusion: Our results contribute to the better understanding of the natural history of BMD and capture precious data in the era of the emerging therapies. The knowledge of the specific DMD mutation may help to define a prognosis in a subset of BMD patients and will serve as a model for the design of future therapies. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Databáze:	MEDLINE
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