Publications

Chosen filters:
Chosen filters:

1 - 10 of 16 results

Sorteren op
Search term:

Identification of the molecular key drivers in disease development in myotonic dystrophy type I. Vrije Universiteit Brussel

Lise Barbé
Myotonic dystrophy type I is the most common muscular dytrophy and is caused by an unstable trinucleotide ‘CTG’ repeat. Due to incomplete understanding of the repeat behaviour, the disease remains incurable. With this thesis, I further characterized two main molecular aspects of the disease being DNA methylation and its role in inheritance of the most severe forms of the disease and the influence of mismatch repair on repeat instability. The ...

Myotonic dystrophy type 1 embryonic stem cells show decreased myogenic potential, increased CpG methylation at the DMPK locus and RNA mis-splicing KU Leuven Vrije Universiteit Brussel

Joke Allemeersch
Skeletal muscle tissue is severely affected in myotonic dystrophy type 1 (DM1) patients, characterised by muscle weakness, myotonia and muscle immaturity in the most severe congenital form of the disease. Previously, it was not known at what stage during myogenesis the DM1 phenotype appears. In this study we differentiated healthy and DM1 human embryonic stem cells to myoblasts and myotubes and compared their differentiation potential using a ...

Genome Editing for Myotonic Dystrophy Type 1. Vrije Universiteit Brussel

Sumitava Dastidar
Myotonic dystrophy type 1 (DM1) is an autosomal dominant neuromuscular disorder with a prevalence ranging from 0.5 to 18.1 per 100,000 individuals. Typically, DM1 patients suffer from progressive myopathy and myotonia, cardiac conduction defects and cognitive impairments. DM1 is caused by the presence of expanded trinucleotide CTG repeats (CTGexp) in the 3’UTR of DMPK gene on ch19q13.3. Expression of the DMPK gene with mutated 3’UTR gives rise ...

Rasch-built myotonic dystrophy type 1 activity and participation scale (DM1-Activ) Hasselt University

Mieke C. E. Hermans, Catharina G. Faber, Christine E. M. de Die-Smulders, Ingemar S. J. Merkies, Marc DE BAETS
We describe the development of an outcome measure of activity and participation for patients with myotonic dystrophy type 1 using the Rasch measurement model. A 49-item questionnaire was completed by 163 DM1 patients. Data were subsequently analyzed with Rasch software to design the item set to fit model expectations. Through systematic investigation of response category ordering, model fit, item bias, and local response dependency, we succeeded ...

CTG repeat instability in a human embryonic stem cell line carrying the myotonic dystrophy type 1 mutation. Vrije Universiteit Brussel

Nele De Temmerman, Sara Seneca, Andre Van Steirteghem, Patrick Haentjens, Josiane Van Der Elst, Ingeborg Liebaers, Karen Sermon
Human embryonic stem cells (hESC) are considered to be an indefinite source of self-renewing cells that can differentiate into all types of cells of the human body and could be used in regenerative medicine, drug discovery and as a model for studying early developmental biology. hESC carrying disease-causing mutations hold promise as a tool to investigate mechanisms involved in the pathogenesis of the disease. In this report, we describe the ...

Chronic endoplasmic reticulum stress in myotonic dystrophy type 2 promotes autoimmunity via mitochondrial DNA release Institute of Tropical Medicine

S Rösing, Fabian Ullrich, S Meisterfeld, Florian Schmidt, L Mlitzko, M Croon, RG Nattrass, N Eberl, J Mahlberg, Martin Schlee, et al.
Myotonic dystrophy type 2 (DM2) is a tetranucleotide CCTG repeat expansion disease associated with an increased prevalence of autoimmunity. Here, we identified an elevated type I interferon (IFN) signature in peripheral blood mononuclear cells and primary fibroblasts of DM2 patients as a trigger of chronic immune stimulation. Although RNA-repeat accumulation was prevalent in the cytosol of DM2-patient fibroblasts, type-I IFN release did not ...

Energy Expenditure, Body Composition, and Skeletal Muscle Oxidative Capacity in Patients with Myotonic Dystrophy Type 1 Vrije Universiteit Brussel

Isis B T Joosten, Cas J Fuchs, Milou Beelen, Guy Plasqui, Luc Van Loon, Catharina G Faber

BACKGROUND: Myotonic dystrophy type 1 (DM1) patients are at risk for metabolic abnormalities and commonly experience overweight and obesity. Possibly, weight issues result from lowered resting energy expenditure (EE) and impaired muscle oxidative metabolism.

OBJECTIVES: This study aims to assess EE, body composition, and muscle oxidative capacity in patients with DM1 compared to age-, sex- and BMI-matched controls.

METHODS: A ...

Human brain pathology in myotonic dystrophy type 1 University of Antwerp

Ralf Weijs, Kees Okkersen, Baziel van Engelen, Benno Kusters, Martin Lammens, Eleonora Aronica, Joost Raaphorst, Anne-Marie van Cappellen van Walsum
Brain involvement in myotonic dystrophy type 1 (DM1) is characterized by heterogeneous cognitive, behavioral, and affective symptoms and imaging alterations indicative of widespread grey and white matter involvement. The aim of the present study was to systematically review the literature on brain pathology in DM1. We conducted a structured search in EMBASE (index period 1974-2017) and MEDLINE (index period 1887-2017) on December 11, 2017, using ...

MSH2 knock-down shows CTG repeat stability and concomitant upstream demethylation at the DMPK locus in myotonic dystrophy type 1 human embryonic stem cells Institute of Tropical Medicine Vrije Universiteit Brussel KU Leuven

Silvie Franck, Lise Barbe, Simon Ardui, Yannick De Vlaeminck, Joke Allemeersch, Dominika Dziedzicka, Claudia Spits, Fien Vanroye, Pierre Hilven, Geoffrey Duque, et al.

Myotonic dystrophy type 1 (DM1) is caused by expansion of a CTG repeat in the DMPK gene, where expansion size and somatic mosaicism correlates with disease severity and age of onset. While it is known that the mismatch repair protein MSH2 contributes to the unstable nature of the repeat, its role on other disease-related features, such as CpG methylation upstream of the repeat, is unknown. In this study, we investigated the effect of an MSH2 ...

Coexistence of progressive supranuclear palsy with pontocerebellar atrophy and myotonic dystrophy type 1 University of Antwerp

Shunsuke Koga, Eric Ahlskog, Michael A. DeTure, Matt Baker, Shanu F. Roemer, Takuya Konno, Rosa Rademakers, Owen A. Ross, Dennis W. Dickson
Progressive supranuclear palsy with predominant cerebellar ataxia (PSP-C) has been reported as a rare clinical subtype, but the underlying pathology of its cerebellar ataxia remains unclear. Here, we report a patient with the coexistence of PSP with pontocerebellar atrophy and myotonic dystrophy type 1 (DM1). A 73-year-old man who was an asymptomatic carrier of DM1 (66 CTG repeats) started developing ataxic gait with multiple falls, visual ...