Variant repeats within the DMPK CTG expansion protect function in myotonic dystrophy type 1

Miller, J. N., van der Plas, E., Hamilton, M., Koscik, T. R., Gutmann, L., Cumming, S. A., Monckton, D. G. and Nopoulos, P. C. (2020) Variant repeats within the DMPK CTG expansion protect function in myotonic dystrophy type 1. Neurology Genetics, 6(5), e504. (doi: 10.1212/NXG.0000000000000504) (PMID:32851192) (PMCID:PMC7428360)

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Abstract

Objective: We tested the hypothesis that variant repeat interruptions (RIs) within the DMPK CTG repeat tract lead to milder symptoms compared with pure repeats (PRs) in myotonic dystrophy type 1 (DM1). Methods: We evaluated motor, neurocognitive, and behavioral outcomes in a group of 6 participants with DM1 with RI compared with a case-matched sample of 12 participants with DM1 with PR and a case-matched sample of 12 unaffected healthy comparison participants (UA). Results: In every measure, the RI participants were intermediate between UA and PR participants. For muscle strength, the RI group was significantly less impaired than the PR group. For measures of Full Scale IQ, depression, and sleepiness, all 3 groups were significantly different from each other with UA > RI > PR in order of impairment. The RI group was different from unaffected, but not significantly different from PR (UA > RI = PR) in apathy and working memory. Finally, in finger tapping and processing speed, RI did not differ from UA comparisons, but PR had significantly lower scores than the UA comparisons (UA = RI > PR). Conclusions: Our results support the notion that patients affected by DM1 with RI demonstrate a milder phenotype with the same pattern of deficits as those with PR indicating a similar disease process.

Item Type:Articles
Additional Information:This work was supported by a grant from the NINDS (Ref: 5R01NS094387-02) and the Wyck Foundation.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cumming, Dr Sarah and Monckton, Professor Darren and Hamilton, Dr Mark
Authors: Miller, J. N., van der Plas, E., Hamilton, M., Koscik, T. R., Gutmann, L., Cumming, S. A., Monckton, D. G., and Nopoulos, P. C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Neurology Genetics
Publisher:Lippincott, Williams & Wilkins
ISSN:2376-7839
ISSN (Online):2376-7839
Published Online:12 August 2020

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