Brain structural features of myotonic dystrophy type 1 and their relationship with CTG repeats

van der Plas, E. et al. (2019) Brain structural features of myotonic dystrophy type 1 and their relationship with CTG repeats. Journal of Neuromuscular Diseases, 6(3), pp. 321-332. (doi: 10.3233/jnd-190397) (PMID:31306140)

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Background: Few adequately-powered studies have systematically evaluated brain morphology in adult-onset myotonic dystrophy type 1 (DM1). Objective: The goal of the present study was to determine structural brain differences between individuals with and without adult-onset DM1 in a multi-site, case-controlled cohort. We also explored correlations between brain structure and CTG repeat length. Methods: Neuroimaging data was acquired in 58 unaffected individuals (29 women) and 79 individuals with DM1 (50 women). CTG repeat length, expressed as estimated progenitor allele length (ePAL), was determined by small pool PCR. Statistical models were adjusted for age, sex, site, and intracranial volume (ICV). Results: ICV was reduced in DM1 subjects compared with controls. Accounting for the difference in ICV, the DM1 group exhibited smaller volume in frontal grey and white matter, parietal grey matter as well as smaller volume of the corpus callosum, thalamus, putamen, and accumbens. In contrast, volumes of the hippocampus and amygdala were significantly larger in DM1. Greater ePAL was associated with lower volumes of the putamen, occipital grey matter, and thalamus. A positive ePAL association was observed for amygdala volume and cerebellar white matter. Conclusions: Smaller ICV may be a marker of aberrant neurodevelopment in adult-onset DM1. Volumetric analysis revealed morphological differences, some associated with CTG repeat length, in structures with plausible links to key DM1 symptoms including cognitive deficits and excessive daytime somnolence. These data offer further insights into the basis of CNS disease in DM1, and highlight avenues for further work to identify therapeutic targets and imaging biomarkers.

Item Type:Articles
Additional Information:Work undertaken in Scotland was funded by Muscular Dystrophy UK (Ref: MC3/1073) and Chief Scientist Office (Ref: CAF/MD/15/01). MJH also received travel awards from the Clinical Genetics Society (UK) and the University of Glasgow (David Fleming-Brown Postgraduate Travel Scholarship) in relation to the work presented here. Research conducted at the Iowa site was funded by a grant from the National Institute of Neurological Disorders and Stroke (NINDS) (Ref: 5R01NS094387-02) and the Wyck Foundation.
Glasgow Author(s) Enlighten ID:Jampana, Dr Ravi and Hamilton, Dr Mark and Monckton, Professor Darren and Cumming, Dr Sarah
Authors: van der Plas, E., Hamilton, M. J., Miller, J. N., Koscik, T. R., Long, J. D., Cumming, S., Povilaikaite, J., Farrugia, M. E., McLean, J., Jampana, R., Magnotta, V. A., Gutmann, L., Monckton, D. G., and Nopoulos, P. C.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Journal of Neuromuscular Diseases
Publisher:IOS Press
ISSN (Online):2214-3602
Copyright Holders:Copyright © 2019 IOS Press and Authors
First Published:First published in Journal of Neuromuscular Diseases 6(3):321-332
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171804Structural CNS changes, neuropsychological impairment and sleep disturbance in type 1 Myotonic dystrophy - a genotype-phenotype studyDarren MoncktonMuscular Dystrophy UK (MUSCDYST)MC3/1073/3MCSB - Molecular Genetics