Muscular Dystrophy

1999 ◽  
Vol 123 (11) ◽  
pp. 1050-1052
Author(s):  
Eric P. Hoffman
Keyword(s):  
Muscular Dystrophy ◽  
Positional Cloning ◽  
Gene Mutations ◽  
Structure And Function ◽  
Disease States ◽  
Membrane Cytoskeleton ◽  
Responsible Gene ◽  
New Frontier ◽  
And Function ◽  
Dystrophin Protein

Abstract The application of cloned genes and their protein products to molecular diagnostics has been an increasingly important area of pathology. The first gene to be identified by positional cloning was the Duchenne muscular dystrophy gene, mutations of which cause one of the most common and most devastating human inherited conditions. The identification of the responsible gene and the encoded dystrophin protein has resulted in a large series of studies concerning the other components of the membrane cytoskeleton of myofibers and their involvement in different forms of muscular dystrophy. Through the study of patients deficient in specific components of the muscle fiber, much is being learned about normal myofiber structure and function and dysfunction in disease states. A new frontier is the application of the normal genes and proteins toward patient therapeutics (gene therapy). Although highly experimental, delivery of therapeutic genes promises to become an important medical practice.

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.

scholarly journals The Duchenne muscular dystrophy gene and cancer

2020 ◽  
Author(s):  
Leanne Jones ◽  
Michael Naidoo ◽  
Lee R. Machado ◽  
Karen Anthony
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Protein ◽  
Neuromuscular Disorders ◽  
Becker Muscular Dystrophy ◽  
Gene Products ◽  
Large Gene ◽  
Cancer Types ◽  
And Function ◽  
Dystrophin Protein

Abstract Background Mutation of the Duchenne muscular dystrophy (DMD) gene causes Duchenne and Becker muscular dystrophy, degenerative neuromuscular disorders that primarily affect voluntary muscles. However, increasing evidence implicates DMD in the development of all major cancer types. DMD is a large gene with 79 exons that codes for the essential muscle protein dystrophin. Alternative promotor usage drives the production of several additional dystrophin protein products with roles that extend beyond skeletal muscle. The importance and function(s) of these gene products outside of muscle are not well understood. Conclusions We highlight a clear role for DMD in the pathogenesis of several cancers, including sarcomas, leukaemia’s, lymphomas, nervous system tumours, melanomas and various carcinomas. We note that the normal balance of DMD gene products is often disrupted in cancer. The short dystrophin protein Dp71 is, for example, typically maintained in cancer whilst the full-length Dp427 gene product, a likely tumour suppressor, is frequently inactivated in cancer due to a recurrent loss of 5’ exons. Therefore, the ratio of short and long gene products may be important in tumorigenesis. In this review, we summarise the tumours in which DMD is implicated and provide a hypothesis for possible mechanisms of tumorigenesis, although the question of cause or effect may remain. We hope to stimulate further study into the potential role of DMD gene products in cancer and the development of novel therapeutics that target DMD.

Novel ABCD1 gene mutations in Iranian pedigrees with X-linked adrenoleukodystrophy

2019 ◽  
Vol 32 (11) ◽  
pp. 1207-1215
Author(s):  
Babak Emamalizadeh ◽  
Yousef Daneshmandpour ◽  
Abbas Tafakhori ◽  
Sakineh Ranji-Burachaloo ◽  
Sajad Shafiee ◽  
...  
Keyword(s):  
Protein Structure ◽  
Direct Sequencing ◽  
Gene Mutations ◽  
Protein Product ◽  
Structure And Function ◽  
Novel Mutations ◽  
Chain Reaction ◽  
Abcd1 Gene ◽  
Polymerase Chain ◽  
And Function

Abstract Background X-linked adrenoleukodystrophy (X-ALD), the most common peroxisomal disorder, is caused by mutations in the ABCD1 gene located on Xq28. X-ALD is characterized by a spectrum of different manifestations varying in patients and families. Methods Four pedigrees with X-ALD consisting of patients and healthy members were selected for investigation of ABCD1 gene mutations. The mutation analysis was performed by polymerase chain reaction (PCR) followed by direct sequencing of all exons. The identified mutations were investigated using bioinformatics tools to predict their effects on the protein product and also to compare the mutated sequence with close species. Results One previously known missense mutation (c.1978 C > T) and three novel mutations (c.1797dupT, c.879delC, c.1218 C > G) were identified in the ABCD1 gene, each in one family. Predicting the effects of the mutations on protein structure and function indicated the probable damaging effect for them with significant alterations in the protein structure. We found three novel mutations in the ABCD1 gene with damaging effects on its protein product and responsible for X-ALD.

Effects of nuclear gene mutations on the structure and function of plastids in pea

Planta ◽  
1982 ◽  
Vol 155 (2) ◽  
pp. 116-123 ◽  
Author(s):  
Hans Paul Schwarz ◽  
Klaus Kloppstech
Keyword(s):  
Gene Mutations ◽  
Nuclear Gene ◽  
Structure And Function ◽  
And Function

Structure and function of masticatory muscles in a case of muscular dystrophy

1990 ◽  
Vol 19 (7) ◽  
pp. 335-340 ◽  
Author(s):  
Merete Bakke ◽  
Svend Kirkeby ◽  
Birgit Leth Jensen ◽  
Hans Jorgen Hansen ◽  
Sven Kreiborg ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Masticatory Muscles ◽  
Structure And Function ◽  
And Function

scholarly journals The lncRNA 44s2 Study Applicability to the Design of 45-55 Exon Skipping Therapeutic Strategy for DMD

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 219
Author(s):  
Elena Gargaun ◽  
Sestina Falcone ◽  
Guilhem Solé ◽  
Julien Durigneux ◽  
Andoni Urtizberea ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Gene Mutations ◽  
Exon Skipping ◽  
Becker Muscular Dystrophy ◽  
Protein Stabilization ◽  
Progressive Muscular Dystrophy ◽  
Dilatative Cardiomyopathy ◽  
Proliferation And Differentiation ◽  
Dmd Gene ◽  
Dystrophin Protein

In skeletal muscle, long noncoding RNAs (lncRNAs) are involved in dystrophin protein stabilization but also in the regulation of myocytes proliferation and differentiation. Hence, they could represent promising therapeutic targets and/or biomarkers for Duchenne and Becker muscular dystrophy (DMD/BMD). DMD and BMD are X-linked myopathies characterized by a progressive muscular dystrophy with or without dilatative cardiomyopathy. Two-thirds of DMD gene mutations are represented by deletions, and 63% of patients carrying DMD deletions are eligible for 45 to 55 multi-exons skipping (MES), becoming BMD patients (BMDΔ45-55). We analyzed the genomic lncRNA presence in 38 BMDΔ45-55 patients and characterized the lncRNA localized in introns 44 and 55 of the DMD gene. We highlighted that all four lncRNA are differentially expressed during myogenesis in immortalized and primary human myoblasts. In addition, the lncRNA44s2 was pointed out as a possible accelerator of differentiation. Interestingly, lncRNA44s expression was associated with a favorable clinical phenotype. These findings suggest that lncRNA44s2 could be involved in muscle differentiation process and become a potential disease progression biomarker. Based on these results, we support MES45-55 therapy and propose that the design of the CRISPR/Cas9 MES45-55 assay consider the lncRNA sequences bordering the exonic 45 to 55 deletion.

scholarly journals Echocardiographic Features of Cardiomyopathy in Emery-Dreifuss Muscular Dystrophy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Michał Marchel ◽  
Agnieszka Madej-Pilarczyk ◽  
Agata Tymińska ◽  
Roman Steckiewicz ◽  
Janusz Kochanowski ◽  
...  
Keyword(s):  
Muscular Dystrophy ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Gene Mutations ◽  
Mitral Annulus ◽  
Control Group ◽  
Rare Type ◽  
Musculoskeletal Abnormalities ◽  
Left And Right ◽  
And Function

Background. Emery-Dreifuss muscular dystrophy (EDMD) is a very rare type of muscular dystrophy characterized by musculoskeletal abnormalities accompanied by cardiac defects. Two most common genetic subtypes are EDMD1 due to EMD and EDMD2 caused by LMNA gene mutations. The aim of the study was to characterize and compare the cardiac morphology and function in the two main genetic subgroups of EDMD with the use of echocardiography. Methods. 41 patients with EDMD (29 EDMD1 and 12 EDMD2) as well as 25 healthy controls were enrolled in our study. Transthoracic echo with the use of a prescribed protocol was performed. Results. Highly statistically significant differences with regard to left ventricle (LV) volumes between the EDMD and the control group were found. 51% of EDMD patients had an enlarged left atrium and as many as 71% had an enlarged right atrium. The LV ejection fraction (LVEF) was significantly lower in EDMD patients than in the control group which corresponded also with a lower systolic velocity of the mitral annulus. 43% of EDMD patients had LVEF below the normal limit. Diastolic dysfunction was detected in 17% of EDMD patients. There were no significant differences between the two types of EDMD in terms of diameters and volumes of any chamber, as well as the systolic function of both left and right ventricles. Conclusions. A significant number of EDMD patients present LV dilatation and different degrees of systolic dysfunction. Dilatation of the atria dominates over ventricle dilatation. We did not present any significant differences between EDMD1 and EDMD2 in terms of the morphology and the function of the heart.

Cell Structure And Function

2012 ◽  
Keyword(s):  
Medical Student ◽  
Cell Structure ◽  
Medical Science ◽  
Normal Structure ◽  
Underlying Disease ◽  
Structure And Function ◽  
Core Knowledge ◽  
Disease States ◽  
Educational Backgrounds ◽  
And Function

Almost every medical student in the United Kingdom, and in many other countries, begins his or her studies with a course on basic cellular structure and function. Such courses are often designed to help students from a variety of educational backgrounds to appreciate the concepts and vocabulary central to all of the life sciences. Over time this core knowledge will be supplemented by other, more specific, areas of medical science until the point is reached at which learners can apply their scientific understanding to those processes of clinical reasoning that lead to diagnosis and treatment. Medical science assists the process of diagnosis by explaining how underlying disease states produce characteristic symptoms and signs. It also facilitates safer treatment by explaining many of the properties, both beneficial and deleterious, of the increasing range of oft en potent therapeutic agents used in clinical management. This chapter poses questions about the basic chemicals of life: proteins, lipids, and carbohydrates. It also covers significant features of the cell membrane and cellular organelles as well as cell division, cellular differentiation, and cell death. Understanding the basic principles of intracellular and intercellular communication and regulation provides the foundation for appreciating the role that these processes play in normal and abnormal neural and hormonal control, which will be considered in more detail in later chapters. All of these topics will eventually contribute to a medical student’s grasp of normal structure and function and how it becomes disturbed in disease. The current chapter also includes questions on basic pharmacokinetics. Knowing how each drug works — that is to say its kinetics and mode of action — is a first step in learning to prescribe safely. Other important principles will be added later in the medical student learning process: for example, the indications and contraindications for the use of a drug; any unwanted side-effects; the route of administration and dosages to produce optimal effects. All of this information must be mastered to help prevent the prescribing errors that are all too common in clinical practice.

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