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

Wenninger, S. et al. (2021) Associations between variant repeat interruptions and clinical outcomes in myotonic dystrophy type 1. Neurology Genetics, 7(2), e572. (doi: 10.1212/NXG.0000000000000572) (PMID:33884298) (PMCID:PMC8054967)

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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 NCT02118779.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Monckton, Professor Darren and Cumming, Dr Sarah
Authors: Wenninger, S., Cumming, S. A., Gutschmidt, K., Okkersen, K., Jimenez-Moreno, A. C., Daidj, F., Lochmüller, H., Hogarth, F., Knoop, H., Bassez, G., Monckton, D. G., van Engelen, B. G.M., and Schoser, B.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Neurology Genetics
Publisher:Lippincott, Williams & Wilkins
ISSN (Online):2376-7839
Published Online:09 March 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Neurology Genetics 7(2): e572
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
167865Observational Prolonged Trial In Myotonic dystrophy type 1 to Improve Stamina, a Target Identification Collaboration (OPTIMISTICDarren MoncktonEuropean Commission (EC)Monckton, Prof DarrenMCSB - Molecular Genetics