The relationship between trinucleotide repeat length and reproductive outcome in myotonic dystrophy type 1 (DM1)

2008 ◽  
Vol 90 ◽  
pp. S304-S305
Author(s):  
W. Verpoest ◽  
S. Seneca ◽  
J. Van der Elst ◽  
P. Haentjens ◽  
P. Devroey ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Trinucleotide Repeat ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Reproductive Outcome ◽  
The Relationship

scholarly journals Increased Muscleblind levels by chloroquine treatment improve myotonic dystrophy type 1 phenotypes in in vitro and in vivo models

2019 ◽  
Vol 116 (50) ◽  
pp. 25203-25213 ◽  
Author(s):  
Ariadna Bargiela ◽  
Maria Sabater-Arcis ◽  
Jorge Espinosa-Espinosa ◽  
Miren Zulaica ◽  
Adolfo Lopez de Munain ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Rna Binding ◽  
Trinucleotide Repeat ◽  
Rna Binding Proteins ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Muscle Area ◽  
In Vivo Models

Myotonic dystrophy type 1 (DM1) is a life-threatening and chronically debilitating neuromuscular disease caused by the expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. The mutant RNA forms insoluble structures capable of sequestering RNA binding proteins of the Muscleblind-like (MBNL) family, which ultimately leads to phenotypes. In this work, we demonstrate that treatment with the antiautophagic drug chloroquine was sufficient to up-regulate MBNL1 and 2 proteins in Drosophila and mouse (HSALR) models and patient-derived myoblasts. Extra Muscleblind was functional at the molecular level and improved splicing events regulated by MBNLs in all disease models. In vivo, chloroquine restored locomotion, rescued average cross-sectional muscle area, and extended median survival in DM1 flies. In HSALR mice, the drug restored muscular strength and histopathology signs and reduced the grade of myotonia. Taken together, these results offer a means to replenish critically low MBNL levels in DM1.

Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1

Neurology ◽  
2004 ◽  
Vol 62 (7) ◽  
pp. 1081-1089 ◽  
Author(s):  
E. L. Logigian ◽  
R. T. Moxley ◽  
C. L. Blood ◽  
C. A. Barbieri ◽  
W. B. Martens ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Ctg Repeat

scholarly journals Intrinsically cell-penetrating multivalent and multitargeting ligands for myotonic dystrophy type 1

2019 ◽  
Vol 116 (18) ◽  
pp. 8709-8714 ◽  
Author(s):  
JuYeon Lee ◽  
Yugang Bai ◽  
Ullas V. Chembazhi ◽  
Shaohong Peng ◽  
Kevin Yum ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Trinucleotide Repeat ◽  
Cell Penetrating Peptides ◽  
Cell Permeability ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Multivalent Ligands ◽  
Biological Studies ◽  
Cell Penetrating

Developing highly active, multivalent ligands as therapeutic agents is challenging because of delivery issues, limited cell permeability, and toxicity. Here, we report intrinsically cell-penetrating multivalent ligands that target the trinucleotide repeat DNA and RNA in myotonic dystrophy type 1 (DM1), interrupting the disease progression in two ways. The oligomeric ligands are designed based on the repetitive structure of the target with recognition moieties alternating with bisamidinium groove binders to provide an amphiphilic and polycationic structure, mimicking cell-penetrating peptides. Multiple biological studies suggested the success of our multivalency strategy. The designed oligomers maintained cell permeability and exhibited no apparent toxicity both in cells and in mice at working concentrations. Furthermore, the oligomers showed important activities in DM1 cells and in a DM1 liver mouse model, reducing or eliminating prominent DM1 features. Phenotypic recovery of the climbing defect in adult DM1Drosophilawas also observed. This design strategy should be applicable to other repeat expansion diseases and more generally to DNA/RNA-targeted therapeutics.

P.35Parental repeat length instability in myotonic dystrophy type 1 pre- and protomutations

2019 ◽  
Vol 29 ◽  
pp. S51
Author(s):  
I. Joosten ◽  
D. Hellebrekers ◽  
B. de Greef ◽  
H. Smeets ◽  
C. de Die-Smulders ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type

scholarly journals Simple Repeat-Primed PCR Analysis of the Myotonic Dystrophy Type 1 Gene in a Clinical Diagnostics Environment

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Philippa A. Dryland ◽  
Elaine Doherty ◽  
Jennifer M. Love ◽  
Donald R. Love
Keyword(s):  
Myotonic Dystrophy ◽  
Trinucleotide Repeat ◽  
Neuromuscular Disorder ◽  
Clinical Diagnostics ◽  
Pcr Analysis ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type ◽  
Diagnostic Laboratory ◽  
Ctg Repeat

Myotonic dystrophy type 1 is an autosomal dominant neuromuscular disorder that is caused by the expansion of a CTG trinucleotide repeat in the DMPK gene. The confirmation of a clinical diagnosis of DM-1 usually involves PCR amplification of the CTG repeat-containing region and subsequent sizing of the amplification products in order to deduce the number of CTG repeats. In the case of repeat hyperexpansions, Southern blotting is also used; however, the latter has largely been superseded by triplet repeat-primed PCR (TP-PCR), which does not yield a CTG repeat number but nevertheless provides a means of stratifying patients regarding their disease severity. We report here a combination of forward and reverse TP-PCR primers that allows for the simple and effective scoring of both the size of smaller alleles and the presence or absence of expanded repeat sequences. In addition, the CTG repeat-containing TP-PCR forward primer can target both the DM-1 and Huntington disease genes, thereby streamlining the work flow for confirmation of clinical diagnoses in a diagnostic laboratory.

scholarly journals Parental repeat length instability in myotonic dystrophy type 1 pre- and protomutations

2020 ◽  
Vol 28 (7) ◽  
pp. 956-962
Author(s):  
Isis B. T. Joosten ◽  
Debby M. E. I. Hellebrekers ◽  
Bianca T. A. de Greef ◽  
Hubert J. M. Smeets ◽  
Christine E. M. de Die-Smulders ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Repeat Length ◽  
Myotonic Dystrophy Type 1 ◽  
Myotonic Dystrophy Type
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