Very Low Residual Dystrophin Quantity Is Associated with Milder Dystrophinopathy

Autor: de Feraudy, Yvan, Ben Yaou, Rabah, Wahbi, Karim, Stalens, Caroline, Stantzou, Amalia, Laugel, Vincent, Desguerre, Isabelle, Servais, Laurent J., Leturcq, France, Amthor, Helge
Přispěvatelé: HAL UVSQ, Équipe, Hôpital Raymond Poincaré [AP-HP], Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Filière Neuromusculaire (FILNEMUS), Association française contre les myopathies (AFM-Téléthon), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de Hautepierre [Strasbourg], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Oxford, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Association Française contre les Myopathies, AFM CDFA‐06‐11 Association Française contre les Myopathies, AFM, This work was supported by the Duchenne Parents Project France, the Association Française Contre les Myopathies, the Association Monegasque Contre les Myopathies, and the Université Franco‐Allemande (CDFA‐06‐11)., CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Oxford [Oxford]
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Annals of Neurology
Annals of Neurology, 2021, 89 (2), pp.280-292. ⟨10.1002/ana.25951⟩
Annals of Neurology, Wiley, 2021, 89 (2), pp.280-292. ⟨10.1002/ana.25951⟩
ISSN: 0364-5134
1531-8249
DOI: 10.1002/ana.25951⟩
Popis: International audience; Objective: This study was undertaken to determine whether a low residual quantity of dystrophin protein is associated with delayed clinical milestones in patients with DMD mutations. Methods: We performed a retrospective multicentric cohort study by using molecular and clinical data from patients with DMD mutations registered in the Universal Mutation Database–DMD France database. Patients with intronic, splice site, or nonsense DMD mutations, with available muscle biopsy Western blot data, were included irrespective of whether they presented with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD). Patients were separated into 3 groups based on dystrophin protein levels. Clinical outcomes were ages at appearance of first symptoms; loss of ambulation; fall in vital capacity and left ventricular ejection fraction; interventions such as spinal fusion, tracheostomy, and noninvasive ventilation; and death. Results: Of 3,880 patients with DMD mutations, 90 with mutations of interest were included. Forty-two patients expressed no dystrophin (group A), and 31 of 42 (74%) developed DMD. Thirty-four patients had dystrophin quantities < 5% (group B), and 21 of 34 (61%) developed BMD. Fourteen patients had dystrophin quantities ≥ 5% (group C), and all but 4 who lost ambulation beyond 24 years of age were ambulant. Dystrophin quantities of
Databáze: OpenAIRE
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