The myotonic dystrophies: molecular, clinical, and therapeutic challenges.

Neuromuscular Research Unit, Tampere University and University Hospital, Tampere, Finland. Electronic address: .
The Lancet Neurology (Impact Factor: 21.82). 10/2012; 11(10):891-905. DOI: 10.1016/S1474-4422(12)70204-1
Source: PubMed

ABSTRACT Myotonic dystrophy is the most common type of muscular dystrophy in adults and is characterised by progressive myopathy, myotonia, and multiorgan involvement. Two genetically distinct entities have been identified. Myotonic dystrophy type 1 (also known as Steinert's disease) was first described more than 100 years ago, whereas myotonic dystrophy type 2 was identified only 18 years ago, after genetic testing for type 1 disease could be applied. Both diseases are caused by autosomal dominant nucleotide repeat expansions. In patients with myotonic dystrophy type 1, a (CTG)(n) expansion is present in DMPK, whereas in patients with type 2 disease, there is a (CCTG)(n) expansion in CNBP. When transcribed into CUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in a spliceopathy of downstream effector genes. The prevailing paradigm therefore is that both disorders are toxic RNA diseases. However, research indicates several additional pathogenic effects take place with respect to protein translation and turnover. Despite clinical and genetic similarities, myotonic dystrophy type 1 and type 2 are distinct disorders requiring different diagnostic and management strategies.


Available from: Ralf Krahe, Apr 28, 2015
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    ABSTRACT: Abstract In this case report we study the dynamics of the SMR band in a subject affected from Facioscapulohumeral Muscular Dystrophy and subjected to Ken Ware Neuro Physics treatment. We use the Generalized Mutual Information (GMI) to analyze in detail the SMR band at rest during the treatment. Brain dynamics responds to a chaotic-deterministic regime with a complex behaviour that constantly self-rearranges and self-organizes such dynamics in function of the outside require- ments. We demonstrate that the SMR chaotic dynamics responds directly to such regime and that also decreasing in EEG during muscular activity really increases its ability of self-arrangement and self-organization in brain. The proposed novel method of the GMI is arranged by us so that it may be used in several cases of clinical interest. In the case of muscular dystrophy here examined, GMI enables us to quantify with accuracy the improvement that the subject realizes during such treatment. Keywords Ken Ware Neuro Physics Treatment, SMR Band, Generalized Mutual Information, Chaotic Brain Dynamics
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    ABSTRACT: Instability and expansion of the DMPK CTG repeat cause myotonic dystrophy type 1 (DM1), the most common adult-onset neuromuscular disorder. Overlapping clinical features between DM1 and other myotonic disorders necessitate molecular confirmation for definitive diagnosis. Preconception screening could improve reproductive planning especially in DM1-affected women, who show diminished ovarian reserve and unfavorable in vitro fertilization-preimplantation genetic diagnosis outcome. We optimized triplet-primed PCR and melting curve analysis on 17 DNAs from DM1-affected/unaffected cell lines. A blinded test was performed on 60 genotype-known clinical samples. Plasmid constructs pDMPK(CTG)35 and pDMPK(CTG)48 were used to establish threshold temperatures separating DM1-affected from unaffected samples. Postscreen triplet-primed PCR amplicon sizing was achieved by short-cycle labeled-primer extension followed by capillary electrophoresis. Triplet-primed PCR melting curve analysis melt peak temperatures of unaffected and DM1-affected samples were lower and higher than the control plasmids' melt peak temperatures, respectively. Capillary electrophoresis of post-melting curve analysis amplicons was completely concordant with the screening results. Triplet-primed PCR melting curve analysis is a simple and cost-effective screening tool for rapid identification of DM1. The companion confirmation protocol allows quick determination of CTG repeat size when required. This strategy avoids the need to perform capillary electrophoresis sizing on all test samples, limiting capillary electrophoresis analysis to only a subset of cases that are screen-positive. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.
    The Journal of molecular diagnostics: JMD 03/2015; 17(2):128-35. DOI:10.1016/j.jmoldx.2014.10.001 · 3.96 Impact Factor
  • 02/2014; DOI:10.1016/j.bjane.2014.01.005