Associations between variant repeat interruptions and clinical outcomes in myotonic dystrophy type 1

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• dc.contributor.author Wenninger, Stephan
• dc.contributor.author Cumming, Sarah A.
• dc.contributor.author Gutschmidt, Kristina
• dc.contributor.author Okkersen, Kees
• dc.contributor.author Jimenez-Moreno, Aura Cecilia
• dc.contributor.author Daidj, Ferroudja
• dc.contributor.author Lochmüller, Hanns
• dc.contributor.author Hogarth, Fiona
• dc.contributor.author Knoop, Hans
• dc.contributor.author Bassez, Guillaume
• dc.contributor.author Monckton, Darren G.
• dc.contributor.author van Engelen, Baziel G.M.
• dc.contributor.author Schoser, Benedikt
• dc.date.accessioned 2021-11-24T07:40:44Z
• dc.date.available 2021-11-24T07:40:44Z
• dc.date.issued 2021
• dc.description.abstract Objective: To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention. Methods: Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory-fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions. Results: VR interruptions were detectable in 21/250 patients (8.4%)-12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions. Conclusions: The presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention. Trial registration information: ClinicalTrials.gov NCT02118779.
• dc.description.sponsorship This study was funded by the European Union Seventh Framework Program, under grant agreement no. 305697 (the Observational Prolonged Trial In Myotonic dystrophy type 1 to Improve Quality of Life Standards, a Target Identification Collaboration [OPTIMISTIC] project) and research fund by the Deutsche Gesellschaft für Muskelkranke e.V. group Germany. D.G. Monckton has been supported by donations from the Myotonic Dystrophy Support Group. S. Wenninger has received research fund by the DGM—Deutsche Gesellschaft für Muskelkranke e.V.
• dc.format.mimetype application/pdf
• dc.identifier.citation Wenninger S, Cumming SA, Gutschmidt K, Okkersen K, Jimenez-Moreno AC, Daidj F, Lochmüller H, Hogarth F, Knoop H, Bassez G, Monckton DG, van Engelen BGM, Schoser B. Associations between variant repeat interruptions and clinical outcomes in myotonic dystrophy type 1. Neurol Genet. 2021;7(2):e572. DOI: 10.1212/NXG.0000000000000572
• dc.identifier.doi http://dx.doi.org/10.1212/NXG.0000000000000572
• dc.identifier.issn 2376-7839
• dc.identifier.uri http://hdl.handle.net/10230/49047
• dc.language.iso eng
• dc.publisher Wolters Kluwer (LWW)
• dc.relation.ispartof Neurol Genet. 2021;7(2):e572
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305697
• dc.rights © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword All Neuropsychology/Behavior
• dc.subject.keyword Clinical trials Randomized controlled (CONSORT agreement)
• dc.subject.keyword Muscle disease
• dc.title Associations between variant repeat interruptions and clinical outcomes in myotonic dystrophy type 1
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion