scholarly journals Dissecting Pathogenetic Mechanisms and Therapeutic Strategies in Drosophila Models of Myotonic Dystrophy Type 1

2018 ◽  
Vol 19 (12) ◽  
pp. 4104 ◽  
Author(s):  
Anissa Souidi ◽  
Monika Zmojdzian ◽  
Krzysztof Jagla
Keyword(s):  
Myotonic Dystrophy ◽  
Heart Defects ◽  
Fruit Fly ◽  
Therapeutic Strategies ◽  
Testicular Atrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Genetic Modifiers ◽  
Multisystemic Disease

Myotonic dystrophy type 1 (DM1), the most common cause of adult-onset muscular dystrophy, is autosomal dominant, multisystemic disease with characteristic symptoms including myotonia, heart defects, cataracts and testicular atrophy. DM1 disease is being successfully modelled in Drosophila allowing to identify and validate new pathogenic mechanisms and potential therapeutic strategies. Here we provide an overview of insights gained from fruit fly DM1 models, either: (i) fundamental with particular focus on newly identified gene deregulations and their link with DM1 symptoms; or (ii) applied via genetic modifiers and drug screens to identify promising therapeutic targets.

scholarly journals MRI findings and cognitive functions in a small cohort of myotonic dystrophy type 1: Retrospective analyses

2016 ◽  
Vol 30 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Arsida Bajrami ◽  
Filiz Azman ◽  
Vildan Yayla ◽  
Sultan Cagirici ◽  
Cahit Keskinkiliç ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Cognitive Deficits ◽  
Morphological Changes ◽  
Brain Mri ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Mri Findings ◽  
Multisystemic Disease ◽  
Systemic Symptoms

Myotonic dystrophy type 1 (DM1) is a progressive multisystemic disease with common cognitive deficits and potential brain involvement in addition to the cardinal muscular and systemic symptoms. Impaired mental function associated with nonspecific pathological findings such as white-matter hyperintense lesions (WMHLs), ventricular enlargement and brain atrophy on brain MRI have been previously reported in DM1 patients. While some studies showed correlation of brain morphological changes with neuropsychological and clinical parameters including CTG repeat sizes and disease severity scales in DM1, others failed. The goal of this study was to retrospectively investigate cranial MR abnormalities, predominantly WMHLs, and their effects on clinical and cognitive deficits in a small, phenotypically or genotypically well-characterized cohort of DM1 patients.

scholarly journals Nuclear Envelope Alterations in Myotonic Dystrophy Type 1 Patient-Derived Fibroblasts

2022 ◽  
Vol 23 (1) ◽  
pp. 522
Author(s):  
Diana Viegas ◽  
Cátia D. Pereira ◽  
Filipa Martins ◽  
Tiago Mateus ◽  
Odete A. B. da Cruz e Silva ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Myotonic Dystrophy ◽  
Molecular Mechanisms ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Protein Levels ◽  
Distal Muscle ◽  
Multisystemic Disease ◽  
And Control

Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease characterized by myotonia, progressive distal muscle weakness and atrophy. The molecular mechanisms underlying this disease are still poorly characterized, although there are some hypotheses that envisage to explain the multisystemic features observed in DM1. An emergent hypothesis is that nuclear envelope (NE) dysfunction may contribute to muscular dystrophies, particularly to DM1. Therefore, the main objective of the present study was to evaluate the nuclear profile of DM1 patient-derived and control fibroblasts and to determine the protein levels and subcellular distribution of relevant NE proteins in these cell lines. Our results demonstrated that DM1 patient-derived fibroblasts exhibited altered intracellular protein levels of lamin A/C, LAP1, SUN1, nesprin-1 and nesprin-2 when compared with the control fibroblasts. In addition, the results showed an altered location of these NE proteins accompanied by the presence of nuclear deformations (blebs, lobes and/or invaginations) and an increased number of nuclear inclusions. Regarding the nuclear profile, DM1 patient-derived fibroblasts had a larger nuclear area and a higher number of deformed nuclei and micronuclei than control-derived fibroblasts. These results reinforce the evidence that NE dysfunction is a highly relevant pathological characteristic observed in DM1.

SEVERE CONGENITAL MYOTONIC DYSTROPHY TYPE 1

2018 ◽  
Vol 97 (1) ◽  
pp. 78-81
Author(s):  
E.A. Mamaeva ◽  
◽  
L.A. Fedorova ◽  
S.E. Voronovich ◽  
V.D. Nazarov ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Congenital Myotonic Dystrophy

scholarly journals What Happened with Muscle Force, Dynamic Stability And Falls?- a 10-Year Longitudinal Follow-Up in Adults with Myotonic Dystrophy Type 1

2021 ◽  
pp. 1-10
Author(s):  
Elisabet Hammarén ◽  
Lena Kollén
Keyword(s):  
Myotonic Dystrophy ◽  
Dynamic Stability ◽  
Muscle Force ◽  
Step Test ◽  
Maximum Speed ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Patient Reported ◽  
Leg Muscle

Background: Individuals with myotonic dystrophy type 1 (DM1) are known to stumble and fall, but knowledge is scarce regarding dynamic stability in this disorder. Objective: To describe disease progress regarding muscle force, dynamic stability and patient reported unintentional falls during a ten-year period, in individuals with DM1. Methods: Quantification of isometric muscle force in four leg muscle groups and assessment of Timed 10-meter-walk in maximum speed (T10max), Timed Up&Go (TUG) and Step test (STEP) were performed at three occasions in a DM1 cohort, together with self-reported falls. Results: Thirty-four people (m/f:11/23, age:50.2 + /–9.4) participated. The muscle force loss after ten years was large in the distal ankle muscles. A steeper force decrease was seen in most muscles between year five and ten compared to the former five-year period. Males reported more falls than females, 91%vs 35%had fallen last year. A positive correlation, ρ= 0.633, p <  0.001, was shown between walking time (T10max) and number of falls. Frequent fallers were only seen among those with slower walk (T10max >  10seconds), and fewer steps in the STEP test (STEP≤5 steps). Conclusions: A diminishing leg muscle strength and worse dynamic stability were seen in the group, with a steeper decrease in the latter five years. Weak ankle dorsiflexors, a slower walk and difficulties to lift the forefoot were related to frequent falls.

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