scholarly journals X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus.

Circulation ◽  
1993 ◽  
Vol 87 (6) ◽  
pp. 1854-1865 ◽  
Author(s):  
J A Towbin ◽  
J F Hejtmancik ◽  
P Brink ◽  
B Gelb ◽  
X M Zhu ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Molecular Genetic ◽  
Dystrophin Gene ◽  
Genetic Evidence ◽  
Molecular Genetic Evidence

Abstract 44: Telomere and Mitochondrial Dysfunction in Duchenne Muscular Dystrophy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Alex C Chang ◽  
Sang-Ging Ong ◽  
Joseph Wu ◽  
Helen M Blau
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Mouse Model ◽  
Dilated Cardiomyopathy ◽  
Mitochondrial Dysfunction ◽  
Telomere Length ◽  
Dystrophin Gene ◽  
Glycoprotein Complex ◽  
The Difference

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disease that is result of mutations in the dystrophin gene and is the most common myopathic disease in humans with a prevalence of one in every 3500 males. Dystrophin is crucial for the formation of a dystrophin-glycoprotein complex (DGC), which connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix in both skeletal and cardiac muscles. In the heart, loss of dystrophin leads to increased fibrosis and death in the third decade of life due to dilated cardiomyopathy. A conundrum in studying and developing therapies for DMD has been the lack of a mouse model that fully recapitulates the clinical phenotype, as mice that lack dystrophin (mdx model), unlike patients, exhibit only mild skeletal muscle defects, essentially no cardiac defects and have a relatively normal lifespan. Our lab reasoned that the difference in the manifestation of the disease in mice and humans could be telomere length, as mice have substantially longer telomeres than humans. We created a novel mouse model with shortened telomere lengths (similar to humans) that fully recapitulates the skeletal muscle (Cell. 2010;143:1059-1071; the mdx/mTRKO model) and cardiac muscle phenotype of DMD (Nat Cell Biol. 2013; 15:895-904; dilated cardiomyopathy). Interestingly, we observed a relative 45% reduction in cardiomyocyte telomere length in our mdx/mTRKO animals (3 animals per group, N = 300-400) as well as patient samples (4 DMD patient samples, N = 40-95). Here we present new evidence of mitochondrial dysfunction and telomere dysfunction.

Molecular genetic evidence of clinical heterogeneity in Fukuyama-type congenital muscular dystrophy

1997 ◽  
Vol 99 (4) ◽  
pp. 427-432 ◽  
Author(s):  
E. Kondo-Iida ◽  
Kayoko Saito ◽  
Hajime Tanaka ◽  
Shoji Tsuji ◽  
Tadayuki Ishihara ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Molecular Genetic ◽  
Congenital Muscular Dystrophy ◽  
Genetic Evidence ◽  
Clinical Heterogeneity ◽  
Molecular Genetic Evidence

scholarly journals Evaluating the potential of novel genetic approaches for the treatment of Duchenne muscular dystrophy

2021 ◽  
Author(s):  
Vratko Himič ◽  
Kay E. Davies
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Structural Integrity ◽  
Viral Vector ◽  
Exon Skipping ◽  
Dystrophin Gene ◽  
Pharmacological Treatments ◽  
Genetic Sequencing ◽  
Reading Frame ◽  
Target Effects

AbstractDuchenne muscular dystrophy (DMD) is an X-linked progressive muscle-wasting disorder that is caused by a lack of functional dystrophin, a cytoplasmic protein necessary for the structural integrity of muscle. As variants in the dystrophin gene lead to a disruption of the reading frame, pharmacological treatments have only limited efficacy; there is currently no effective therapy and consequently, a significant unmet clinical need for DMD. Recently, novel genetic approaches have shown real promise in treating DMD, with advancements in the efficacy and tropism of exon skipping and surrogate gene therapy. CRISPR-Cas9 has the potential to be a ‘one-hit’ curative treatment in the coming decade. The current limitations of gene editing, such as off-target effects and immunogenicity, are in fact partly constraints of the delivery method itself, and thus research focus has shifted to improving the viral vector. In order to halt the loss of ambulation, early diagnosis and treatment will be pivotal. In an era where genetic sequencing is increasingly utilised in the clinic, genetic therapies will play a progressively central role in DMD therapy. This review delineates the relative merits of cutting-edge genetic approaches, as well as the challenges that still need to be overcome before they become clinically viable.

scholarly journals Autophagy in the heart is enhanced and independent of disease progression in mus musculus dystrophinopathy models

2019 ◽  
Vol 8 ◽  
pp. 204800401987958
Author(s):  
HR Spaulding ◽  
C Ballmann ◽  
JC Quindry ◽  
MB Hudson ◽  
JT Selsby
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disease Progression ◽  
Gene Mutations ◽  
Dystrophin Gene ◽  
Mdx Mice ◽  
Dystrophin Deficiency ◽  
Muscle Wasting Disease ◽  
Dystrophin Protein

Background Duchenne muscular dystrophy is a muscle wasting disease caused by dystrophin gene mutations resulting in dysfunctional dystrophin protein. Autophagy, a proteolytic process, is impaired in dystrophic skeletal muscle though little is known about the effect of dystrophin deficiency on autophagy in cardiac muscle. We hypothesized that with disease progression autophagy would become increasingly dysfunctional based upon indirect autophagic markers. Methods Markers of autophagy were measured by western blot in 7-week-old and 17-month-old control (C57) and dystrophic (mdx) hearts. Results Counter to our hypothesis, markers of autophagy were similar between groups. Given these surprising results, two independent experiments were conducted using 14-month-old mdx mice or 10-month-old mdx/Utrn± mice, a more severe model of Duchenne muscular dystrophy. Data from these animals suggest increased autophagosome degradation. Conclusion Together these data suggest that autophagy is not impaired in the dystrophic myocardium as it is in dystrophic skeletal muscle and that disease progression and related injury is independent of autophagic dysfunction.

A carrier of Duchenne muscular dystrophy with dilated cardiomyopathy but no skeletal muscle symptom

1995 ◽  
Vol 17 (3) ◽  
pp. 202-205 ◽  
Author(s):  
Hirotoshi Kinoshita ◽  
Yu-ichi Goto ◽  
Mitsuru Ishikawa ◽  
Tetsuya Uemura ◽  
Kouichi Matsumoto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy ◽  
Muscle Symptom

scholarly journals Molecular Genetic Evidence for the Role of SGT1 in the Intramolecular Complementation of Bs2 Protein Activity in Nicotiana benthamiana

2005 ◽  
Vol 17 (4) ◽  
pp. 1268-1278 ◽  
Author(s):  
R. Todd Leister ◽  
Douglas Dahlbeck ◽  
Brad Day ◽  
Yi Li ◽  
Olga Chesnokova ◽  
...  
Keyword(s):  
Nicotiana Benthamiana ◽  
Molecular Genetic ◽  
Genetic Evidence ◽  
Protein Activity ◽  
Molecular Genetic Evidence

Molecular genetic evidence supporting a novel human hepatocellular carcinoma tumor suppressor locus at 13q12.11

2005 ◽  
Vol 44 (3) ◽  
pp. 320-328 ◽  
Author(s):  
Chian-Feng Chen ◽  
Shiou-Hwei Yeh ◽  
Ding-Shinn Chen ◽  
Pei-Jer Chen ◽  
Yuh-Shan Jou
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Suppressor ◽  
Molecular Genetic ◽  
Human Hepatocellular Carcinoma ◽  
Genetic Evidence ◽  
Molecular Genetic Evidence ◽  
Carcinoma Tumor

Molecular genetic evidence for the conversion hypothesis of the origin of malignant mixed Müllerian tumours

1997 ◽  
Vol 183 (4) ◽  
pp. 424-431 ◽  
Author(s):  
Edwin C. A. Abeln ◽  
Vincent T. H. B. M. Smit ◽  
Johannes W. Wessels ◽  
Wiljo J. F. de Leeuw ◽  
Cees J. Cornelisse ◽  
...  
Keyword(s):  
Molecular Genetic ◽  
Genetic Evidence ◽  
Molecular Genetic Evidence

Effect of Ivabradine in dilated cardiomyopathy from Duchenne muscular dystrophy: A chance for slowing progression of heart failure?

2016 ◽  
Vol 223 ◽  
pp. 286-288 ◽  
Author(s):  
Giuseppina De Benedittis ◽  
Giulia Della Rosa ◽  
Enzo D'Ettorre ◽  
Prisco Piscitelli ◽  
Alessandro Distante ◽  
...  
Keyword(s):  
Heart Failure ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Dilated Cardiomyopathy
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