Journal articles: 'Dystrophie musculaire de Becker'

1

Opoko, A. P., A. Labied, S. El Moussaoui, and G. Belmejdoub. "Dystrophie musculaire de Becker et acromégalie : association fortuite." Annales d'Endocrinologie 75, no. 5-6 (October 2014): 424. http://dx.doi.org/10.1016/j.ando.2014.07.514.

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Dahimène, Fayçal, Julien Durigneux, Aleksandra Nadaj, Sandra Mercier, Yann Péréon, and Armelle Magot. "Cas clinique 3 : dystrophie musculaire de Becker et atteinte cognitive." Revue Neurologique 174 (April 2018): S179. http://dx.doi.org/10.1016/j.neurol.2018.02.052.

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Magot, A., S. Mercier, and Y. Péréon. "Particularités de la dystrophie musculaire de Becker et des femmes conductrices." Archives de Pédiatrie 22, no. 12 (December 2015): 12S31–12S36. http://dx.doi.org/10.1016/s0929-693x(16)30006-9.

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Lescaut, W., C. Butori, M. H. Soriani, and C. Desnuelles. "À propos de quatre cas féminins de dystrophie musculaire de Duchenne et Becker." La Revue de Médecine Interne 25, no. 6 (June 2004): 464–67. http://dx.doi.org/10.1016/j.revmed.2004.03.001.

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Allart, M. E., M. N. Olivier, V. Wieczorek, H. Hovart, A. Thevenon, and V. Tiffreau. "Évaluation de l’oxygénation musculaire à l’effort chez des patients porteurs de dystrophie musculaire de Becker par la spectroscopie du proche infrarouge (NIRS)." Annals of Physical and Rehabilitation Medicine 54 (October 2011): e152. http://dx.doi.org/10.1016/j.rehab.2011.07.523.

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Tselikas, L., E. Rodrigues, M. Jammal, K. Tiev, C. Chayet, L. Josselin-Mahr, M. Gain, C. Toledano, J. Cabane, and A. Kettaneh. "Dystrophie musculaire de Becker à révélation tardive. À propos d’un nouveau patient et de 12 observations de la littérature." La Revue de Médecine Interne 32, no. 3 (March 2011): 181–86. http://dx.doi.org/10.1016/j.revmed.2010.10.353.

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Srivastava, Niraj Kumar, Somnath Mukherjee, and Vijay Nath Mishra. "Metabolic Disturbance in Patients with Muscular Dystrophy and Reflection of Altered Enzyme Activity in Dystrophic Muscle: One Critical View." Journal of Biomedical Research & Environmental Sciences 1, no. 8 (December 2020): 393–403. http://dx.doi.org/10.37871/jbres1171.

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Muscular dystrophies are inherited myogenic diseases and considered by progressive muscle wasting and weakness with variable distribution and severity. The essential characteristics of muscular dystrophies are selective involvement, significant wasting and weakness of muscles. The most common and frequent types of muscular dystrophies are Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Facioscapulohumeral Dystrophy (FSHD) and Limb Girdle Muscular Dystrophy (LGMD). Metabolic disturbance is observed in muscular dystrophy patients (DMD, BMD, FSHD and LGMD-2B). Alteration in the level of metabolites (BCAA, Glu/ Gln, Ace, alanine, glucose, histidine, propionate, tyrosine and fumarate) in dystrophic muscle reflects the alteration in the activity of enzymes. Collectively, these observations propose that there is alteration in the rate of glycolysis, TCA cycle, fatty acid oxidation, gluconeogenesis pathway and protein metabolism (catabolism & anabolism) in the muscular dystrophy patients. Metabolic disturbance, further provide the explanation about the pathophysiology of muscular dystrophy.

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Teramoto, Naomi, Hidetoshi Sugihara, Keitaro Yamanouchi, Katsuyuki Nakamura, Koichi Kimura, Tomoko Okano, Takanori Shiga, et al. "Pathological evaluation of rats carrying in-frame mutations in the dystrophin gene: a new model of Becker muscular dystrophy." Disease Models & Mechanisms 13, no. 9 (August 28, 2020): dmm044701. http://dx.doi.org/10.1242/dmm.044701.

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ABSTRACTDystrophin, encoded by the DMD gene on the X chromosome, stabilizes the sarcolemma by linking the actin cytoskeleton with the dystrophin-glycoprotein complex (DGC). In-frame mutations in DMD cause a milder form of X-linked muscular dystrophy, called Becker muscular dystrophy (BMD), characterized by the reduced expression of truncated dystrophin. So far, no animal model with in-frame mutations in Dmd has been established. As a result, the effect of in-frame mutations on the dystrophin expression profile and disease progression of BMD remains unclear. In this study, we established a novel rat model carrying in-frame Dmd gene mutations (IF rats) and evaluated the pathology. We found that IF rats exhibited reduced expression of truncated dystrophin in a proteasome-independent manner. This abnormal dystrophin expression caused dystrophic changes in muscle tissues but did not lead to functional deficiency. We also found that the expression of additional dystrophin named dpX, which forms the DGC in the sarcolemma, was associated with the appearance of truncated dystrophin. In conclusion, the outcomes of this study contribute to the further understanding of BMD pathology and help elucidate the efficiency of dystrophin recovery treatments in Duchenne muscular dystrophy, a more severe form of X-linked muscular dystrophy.

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Sarkozy, Anna, Mariacristina Scoto, Francesco Muntoni, and Joana Domingos. "Dystrophinopathies and Limb-Girdle Muscular Dystrophies." Neuropediatrics 48, no. 04 (April 20, 2017): 262–72. http://dx.doi.org/10.1055/s-0037-1601860.

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AbstractMuscular dystrophies are a heterogeneous group of inherited diseases. The natural history of these disorders along with their management have changed mainly due to a better understanding of their pathophysiology, the evolution of standards of care, and new treatment options. Dystrophinopathies include both Duchenne's and Becker's muscular dystrophies, but in reality they are a spectrum of muscle diseases caused by mutations in the gene that encodes the protein dystrophin. Duchenne's muscular dystrophy is the most common form of inherited muscle disease of childhood. The current standards of care considerably prolong independent ambulation and survival. Several therapeutic options either aiming at substituting/correcting the primary protein defect or limiting the progression of the dystrophic process are currently being explored in clinical trials.Limb-girdle muscular dystrophies (LGMDs) are rare and heterogeneous conditions, characterized by weakness and wasting of the pelvic and shoulder girdle muscles. Originally classified into dominant and recessive, > 30 genetic forms of LGMDs are currently recognized. Further understanding of the pathogenic mechanisms of LGMD will help identifying novel therapeutic approaches that can be tested in clinical trials.

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Bellayou, Hanane, Khalil Hamzi, Mohamed Abdou Rafai, Mehdi Karkouri, Ilham Slassi, Houssine Azeddoug, and Sellama Nadifi. "Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco." Journal of Biomedicine and Biotechnology 2009 (2009): 1–5. http://dx.doi.org/10.1155/2009/325210.

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Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis.

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Assereto, Stefania, Silvia Stringara, Federica Sotgia, Gloria Bonuccelli, Aldobrando Broccolini, Marina Pedemonte, Monica Traverso, et al. "Pharmacological rescue of the dystrophin-glycoprotein complex in Duchenne and Becker skeletal muscle explants by proteasome inhibitor treatment." American Journal of Physiology-Cell Physiology 290, no. 2 (February 2006): C577—C582. http://dx.doi.org/10.1152/ajpcell.00434.2005.

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In this report, we have developed a novel method to identify compounds that rescue the dystrophin-glycoprotein complex (DGC) in patients with Duchenne or Becker muscular dystrophy. Briefly, freshly isolated skeletal muscle biopsies (termed skeletal muscle explants) from patients with Duchenne or Becker muscular dystrophy were maintained under defined cell culture conditions for a 24-h period in the absence or presence of a specific candidate compound. Using this approach, we have demonstrated that treatment with a well-characterized proteasome inhibitor, MG-132, is sufficient to rescue the expression of dystrophin, β-dystroglycan, and α-sarcoglycan in skeletal muscle explants from patients with Duchenne or Becker muscular dystrophy. These data are consistent with our previous findings regarding systemic treatment with MG-132 in a dystrophin-deficient mdx mouse model (Bonuccelli G, Sotgia F, Schubert W, Park D, Frank PG, Woodman SE, Insabato L, Cammer M, Minetti C, and Lisanti MP. Am J Pathol 163: 1663–1675, 2003). Our present results may have important new implications for the possible pharmacological treatment of Duchenne or Becker muscular dystrophy in humans.

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Esposito, Gabriella, and Antonella Carsana. "Metabolic Alterations in Cardiomyocytes of Patients with Duchenne and Becker Muscular Dystrophies." Journal of Clinical Medicine 8, no. 12 (December 5, 2019): 2151. http://dx.doi.org/10.3390/jcm8122151.

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Duchenne and Becker muscular dystrophies (DMD/BMD) result in progressive weakness of skeletal and cardiac muscles due to the deficiency of functional dystrophin. Respiratory failure is a leading cause of mortality in DMD patients; however, improved management of the respiratory symptoms have increased patients’ life expectancy, thereby also increasing the clinical relevance of heart disease. In fact, the prevalence of cardiomyopathy, which significantly contributes to mortality in DMD patients, increases with age and disease progression, so that over 95% of adult patients has cardiomyopathy signs. We here review the current literature featuring the metabolic alterations observed in the dystrophic heart of the mdx mouse, i.e., the best-studied animal model of the disease, and discuss their pathophysiological role in the DMD heart. It is well assessed that dystrophin deficiency is associated with pathological alterations of lipid metabolism, intracellular calcium levels, neuronal nitric oxide (NO) synthase localization, and NO and reactive oxygen species production. These metabolic stressors contribute to impair the function of the cardiac mitochondrial bulk, which has a relevant pathophysiological role in the development of cardiomyopathy. In fact, mitochondrial dysfunction becomes more severe as the dystrophic process progresses, thereby indicating it may be both the cause and the consequence of the dystrophic process in the DMD heart.

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Saotome, Masao, Yuji Yoshitomi, Shunichi Kojima, and Morio Kuramochi. "Dilated Cardiomyopathy of Becker-Type Muscular Dystrophy with Exon 4 Deletion." Angiology 52, no. 5 (May 2001): 343–47. http://dx.doi.org/10.1177/000331970105200508.

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The authors report a 47-year-old man with Becker-type muscular dystrophy presenting with dilated cardiomyopathy. Left ventriculography showed diffuse severe hypokinesia: left ventric ular end-diastolic volume index 193 mL/m2, left ventricular end-systolic volume index 143 mL/m 2, and left ventricular ejection fraction 26%. Skeletal muscle biopsy demonstrated a dystrophic process. Genetic analysis revealed a deletion of exon 4. There was a difference in immunos taining pattern between skeletal muscles and cardiac muscles. Severe cardiac dysfunction in this case may be associated with the damage in dystrophin-deficient fibers.

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Freund, Aline Andrade, Rosana Herminia Scola, Raquel Cristina Arndt, Paulo José Lorenzoni, Claudia Kamoy Kay, and Lineu Cesar Werneck. "Duchenne and Becker muscular dystrophy: a molecular and immunohistochemical approach." Arquivos de Neuro-Psiquiatria 65, no. 1 (March 2007): 73–76. http://dx.doi.org/10.1590/s0004-282x2007000100016.

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Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are caused by mutations in the dystrophin gene. We studied 106 patients with a diagnosis of probable DMD/BMD by analyzing 20 exons of the dystrophin gene in their blood and, in some of the cases, by immunohistochemical assays for dystrophin in muscle biopsies. In 71.7% of the patients, deletions were found in at least one of the exons; 68% of these deletions were in the hot-spot 3' region. Deletions were found in 81.5% of the DMD cases and in all the BMD cases. The cases without deletions, which included the only woman in the study with DMD, had dystrophin deficiency. The symptomatic female carriers had no deletions but had abnormal dystrophin distribution in the sarcolemma (discontinuous immunostains). The following diagnoses were made for the remaining cases without deletions with the aid of a muscle biopsy: spinal muscular atrophy, congenital myopathy; sarcoglycan deficiency and unclassified limb-girdle muscular dystrophy. Dystrophin analysis by immunohistochemistry continues to be the most specific method for diagnosis of DMD/BMD and should be used when no exon deletions are found in the dystrophin gene in the blood.

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Niebrój-Dobosz, Irena, and Irena Hausmanowa-Petrusewicz. "The involvement of oxidative stress in determining the severity and progress of pathological processes in dystrophin-deficient muscles." Acta Biochimica Polonica 52, no. 2 (May 25, 2005): 449–52. http://dx.doi.org/10.18388/abp.2005_3458.

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In both forms of muscular dystrophy, the severe Duchenne's muscular dystrophy (DMD) with lifespan shortened to about 20 years and the milder Becker dystrophy (BDM) with normal lifespan, the gene defect is located at chromosome locus Xp21. The location is the same in the experimental model of DMD in the mdx mice. As the result of the gene defect a protein called dystrophin is either not synthesized, or is produced in traces. Although the structure of this protein is rather well established there are still many controversies about the dystrophin function. The most accepted suggestion supposes that it stabilizes sarcolemma in the course of the contraction-relaxation cycle. Solving the problem of dystrophin function is a prerequisite for introduction of an effective therapy. Among the different factors which might be responsible for the appearance and progress of dystrophic changes in muscles there is an excessive action of oxidative stress. In this review data indicating the influence of oxidative stress on the severity of the pathologic processes in dystrophy are discussed. Several pieces of data indicating the action of oxidative damage to different macromolecules in DMD/BDM are presented. Special attention is devoted to the degree of oxidative damage to muscle proteins, the activity of neuronal nitric oxide synthase (nNOS) and their involvement in defining the severity of the dystrophic processes. It is indicated that the severity of the morbid process is related to the degree of oxidative damage to muscle proteins and the decrease of the nNOS activity in muscles. Estimation of the degree of the destructive action of oxidative stress in muscular dystrophy may be a useful marker facilitating introduction of an effective antioxidant therapy and regulation of nNOS activity.

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Menke, A., and H. Jockusch. "Extent of shock-induced membrane leakage in human and mouse myotubes depends on dystrophin." Journal of Cell Science 108, no. 2 (February 1, 1995): 727–33. http://dx.doi.org/10.1242/jcs.108.2.727.

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A lack of the cytoskeletal protein dystrophin causes muscle fiber necrosis in Duchenne/Becker muscular dystrophies (DMD/BMD) and in murine X-linked muscular dystrophy (MDX). However, no overt disease symptoms are observed in dystrophin-less cultured myotubes, and the biological function of dystrophin in normal muscle cells is still unknown. In this work, we have extended our studies on a model system, using hypoosmotic shock to determine stress resistance of muscle cells. In frozen sections of control human and mouse myotubes, dystrophin was shown to be localized at the cell periphery as in mature muscle fibers. Dystrophin-less DMD and MDX myotubes were more susceptible to hypoosmotic shock than controls, as monitored by the uptake of external horseradish peroxidase and release of the soluble enzymes creatinine kinase or pyruvate kinase and of radiolabelled proteins. Control experiments indicated that this difference is not due to differences in metabolism or ion fluxes. Treatment with cytochalasin D drastically increased the shock sensitivity of myotubes and abolished the difference between dystrophin-less and control cells. These results lend further support to the suggested stabilizing role of dystrophin in the context of the membrane-cytoskeletal complex.

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Bkaily, Ghassan, and Danielle Jacques. "Na+–H+ exchanger and proton channel in heart failure associated with Becker and Duchenne muscular dystrophies." Canadian Journal of Physiology and Pharmacology 95, no. 10 (October 2017): 1213–23. http://dx.doi.org/10.1139/cjpp-2017-0265.

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Cardiomyopathy is found in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies, which are linked muscle diseases caused by mutations in the dystrophin gene. Dystrophin defects are not limited to DMD but are also present in mild BMD. The hereditary cardiomyopathic hamster of the UM-X7.1 strain is a particular experimental model of heart failure (HF) leading to early death in muscular dystrophy (dystrophin deficiency and sarcoglycan mutation) and heart disease (δ-sarcoglycan deficiency and dystrophin mutation) in human DMD. Using this model, our previous work showed a defect in intracellular sodium homeostasis before the appearance of any apparent biochemical and histological defects. This was attributed to the continual presence of the fetal slow sodium channel, which was also found to be active in human DMD. Due to muscular intracellular acidosis, the intracellular sodium overload in DMD and BMD was also due to sodium influx through the sodium–hydrogen exchanger NHE-1. Lifetime treatment with an NHE-1 inhibitor prevented intracellular Na+ overload and early death due to HF. Our previous work also showed that another proton transporter, the voltage-gated proton channel (Hv1), exists in many cell types including heart cells and skeletal muscle fibers. The Hv1 could be indirectly implicated in the beneficial effect of blocking NHE-1.

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Hodges, B. L., Y. K. Hayashi, I. Nonaka, W. Wang, K. Arahata, and S. J. Kaufman. "Altered expression of the alpha7beta1 integrin in human and murine muscular dystrophies." Journal of Cell Science 110, no. 22 (November 15, 1997): 2873–81. http://dx.doi.org/10.1242/jcs.110.22.2873.

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The alpha7beta1 integrin is the primary laminin receptor on skeletal myoblasts and adult myofibers. It has distinct functions during muscle development and contributes to muscle structural integrity. We have studied this integrin in cases where expression of dystrophin or laminin are compromised. Immunofluorescence demonstrates an increase in alpha7beta1 in patients with Duchenne muscular dystrophy and in mdx mice that lack dystrophin. Analysis of RNA from mdx mice and from patients with Duchenne and Becker muscular dystrophies indicates that the increase in the alpha7beta1 integrin is regulated at the level of alpha7 gene transcription. In contrast, the levels of alpha7beta1 integrin are severely diminished in patients with laminin alpha2 chain congenital dystrophy muscular dystrophy and in dy/dy mice that also do not make the alpha2 laminin chain. Analysis of RNA from the hindlimbs of dy/dy mice demonstrated that in the absence of laminin alpha7 gene transcription is inhibited and limited to specific alternatively spliced isoforms. We suggest that the increased expression of alpha7beta1 integrin in the absence of dystrophin compensates for the reduced dystrophin-mediated linkage of fibers with the basal lamina and modulates the development of pathology associated with these diseases. The decrease in alpha7beta1 integrin and its transcripts in the absence of laminin likely contributes to the severe myopathy that results from laminin alpha2 chain deficiency and suggests that laminin-2 regulates expression of the alpha7 integrin gene. The role of the alpha7beta1 integrin in muscle integrity also suggests that compromised expression of this receptor may underlie as yet undefined myopathies.

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Guiraud, Simon, Benjamin Edwards, Arran Babbs, Sarah E. Squire, Adam Berg, Lee Moir, Matthew J. Wood, and Kay E. Davies. "The potential of utrophin and dystrophin combination therapies for Duchenne muscular dystrophy." Human Molecular Genetics 28, no. 13 (March 5, 2019): 2189–200. http://dx.doi.org/10.1093/hmg/ddz049.

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Abstract Duchenne muscular dystrophy (DMD) is a lethal neuromuscular disorder caused by loss of dystrophin. Several therapeutic modalities are currently in clinical trials but none will achieve maximum functional rescue and full disease correction. Therefore, we explored the potential of combining the benefits of dystrophin with increases of utrophin, an autosomal paralogue of dystrophin. Utrophin and dystrophin can be co-expressed and co-localized at the same muscle membrane. Wild-type (wt) levels of dystrophin are not significantly affected by a moderate increase of utrophin whereas higher levels of utrophin reduce wt dystrophin, suggesting a finite number of actin binding sites at the sarcolemma. Thus, utrophin upregulation strategies may be applied to the more mildly affected Becker patients with lower dystrophin levels. Whereas increased dystrophin in wt animals does not offer functional improvement, overexpression of utrophin in wt mice results in a significant supra-functional benefit over wt. These findings highlight an additive benefit of the combined therapy and potential new unique roles of utrophin. Finally, we show a 30% restoration of wt dystrophin levels, using exon-skipping, together with increased utrophin levels restores dystrophic muscle function to wt levels offering greater therapeutic benefit than either single approach alone. Thus, this combination therapy results in additive functional benefit and paves the way for potential future combinations of dystrophin- and utrophin-based strategies.

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Corrado, K., J. A. Rafael, P. L. Mills, N. M. Cole, J. A. Faulkner, K. Wang, and J. S. Chamberlain. "Transgenic mdx mice expressing dystrophin with a deletion in the actin-binding domain display a "mild Becker" phenotype." Journal of Cell Biology 134, no. 4 (August 15, 1996): 873–84. http://dx.doi.org/10.1083/jcb.134.4.873.

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The functional significance of the actin-binding domain of dystrophin, the protein lacking in patients with Duchenne muscular dystrophy, has remained elusive. Patients with deletions of this domain (domain I) typically express low levels of the truncated protein. Whether the moderate to severe phenotypes associated with such deletions result from loss of an essential function, or from reduced levels of a functional protein, is unclear. To address this question, we have generated transgenic mice that express wild-type levels of a dystrophin deleted for the majority of the actin-binding domain. The transgene derived protein lacks amino acids 45-273, removing 2 of 3 in vitro identified actin interacting sites and part of hinge 1. Examination of the effect of this deletion in mice lacking wild-type dystrophin (mdx) suggests that a functional domain I is not essential for prevention of a dystrophic phenotype. However, in contrast to deletions in the central rod domain and to full-length dystrophin, both of which are functional at only 20% of wild-type levels, proteins with a deletion in domain I must be expressed at high levels to prevent a severe dystrophy. These results are also in contrast to the severe dystrophy resulting from truncation of the COOH-terminal domain that links dystrophin to the extracellular matrix. The mild phenotype observed in mice with domain I-deletions indicates that an intact actin-binding domain is not essential, although it does contribute to an important function of dystrophin. These studies also suggest the link between dystrophin and the subsarcolemmal cytoskeleton involves more than a simple attachment of domain I to actin filaments.

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Schnell, Frederick J., Diane Frank, Sue Fletcher, Russell D. Johnsen, and Steve D. Wilton. "Challenges of Interpreting Dystrophin Content by Western Blot." US Neurology 15, no. 1 (2019): 40. http://dx.doi.org/10.17925/usn.2019.15.1.40.

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The Duchenne muscular dystrophy community has recently seen the first approved therapy for the restoration of dystrophin, based on its ability to increase levels of dystrophin protein, as determined by western blot. The approval, along with the initiation of clinical trials evaluating other dystrophin-restoring therapies, highlights the importance of accurate dystrophin quantitation. Nonoptimized western blot methods can reflect inaccurate results, especially in the quantitation of low dystrophin levels. A few key changes to standards and data analysis parameters can result in a low level of dystrophin (<0.5% of a healthy biopsy) being inaccurately interpreted as >20% of the levels reported in healthy human muscle. A review of the dystrophin western blot data on Duchenne and Becker muscular dystrophy biopsies is conducted, along with a thorough investigation of methodologies to quantify dystrophin.

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McARDLE, Anne, Timothy R. HELLIWELL, Geoffrey J. BECKETT, Mariana CATAPANO, Anthony DAVIS, and Malcolm J. JACKSON. "Effect of propylthiouracil-induced hypothyroidism on the onset of skeletal muscle necrosis in dystrophin-deficient mdx mice." Clinical Science 95, no. 1 (July 1, 1998): 83–89. http://dx.doi.org/10.1042/cs0950083.

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1.Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (< 3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2.This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3.Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4.The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.

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Nakamura, Akinori. "Mutation-Based Therapeutic Strategies for Duchenne Muscular Dystrophy: From Genetic Diagnosis to Therapy." Journal of Personalized Medicine 9, no. 1 (March 4, 2019): 16. http://dx.doi.org/10.3390/jpm9010016.

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Duchenne and Becker muscular dystrophy (DMD/BMD) are X-linked muscle disorders caused by mutations of the DMD gene, which encodes the subsarcolemmal protein dystrophin. In DMD, dystrophin is not expressed due to a disruption in the reading frame of the DMD gene, resulting in a severe phenotype. Becker muscular dystrophy exhibits a milder phenotype, having mutations that maintain the reading frame and allow for the production of truncated dystrophin. To date, various therapeutic approaches for DMD have been extensively developed. However, the pathomechanism is quite complex despite it being a single gene disorder, and dystrophin is expressed not only in a large amount of skeletal muscle but also in cardiac, vascular, intestinal smooth muscle, and nervous system tissue. Thus, the most appropriate therapy would be complementation or restoration of dystrophin expression, such as gene therapy using viral vectors, readthrough therapy, or exon skipping therapy. Among them, exon skipping therapy with antisense oligonucleotides can restore the reading frame and yield the conversion of a severe phenotype to one that is mild. In this paper, I present the significance of molecular diagnosis and the development of mutation-based therapeutic strategies to complement or restore dystrophin expression.

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Mah, Jean K., Lawrence Korngut, Kirsten M. Fiest, Jonathan Dykeman, Lundy J. Day, Tamara Pringsheim, and Nathalie Jette. "A Systematic Review and Meta-analysis on the Epidemiology of the Muscular Dystrophies." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 43, no. 1 (November 24, 2015): 163–77. http://dx.doi.org/10.1017/cjn.2015.311.

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AbstractBackground: The muscular dystrophies are a heterogeneous group of genetic muscle diseases with variable distribution of weakness and mode of inheritance.Methods: We previously performed a systematic review of worldwide population-based studies on Duchenne and Becker muscular dystrophies; the current study focused on the epidemiology of other muscular dystrophies using Medline and EMBASE databases. Two reviewers independently reviewed all abstracts, full-text articles, and abstracted data from 1985 to 2011. Pooling of prevalence estimates was performed using random-effect models.Results: A total of 1104 abstracts and 167 full-text articles were reviewed. Thirty-one studies met all eligibility criteria and were included in the final analysis. The overall pooled prevalence of combined muscular dystrophies was 16.14 (confidence interval [CI], 11.21-23.23) per 100,000. The prevalence estimates per 100,000 were 8.26 (CI, 4.99-13.68) for myotonic dystrophy, 3.95 (CI, 2.89-5.40) for facioscapulohumeral dystrophy, 1.63 (CI, 0.94-2.81) for limb girdle muscular dystrophy, and 0.99 (CI, 0.62-1.57) for congenital muscular dystrophies.Conclusions: The studies differed widely in their approaches to case ascertainment, and substantial gaps remain in the global estimates of many other types of muscular dystrophies. Additional epidemiological studies using standardized diagnostic criteria as well as multiple sources of case ascertainment will help address the economic impact and health care burden of muscular dystrophies worldwide.

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Chao, D. S., J. R. Gorospe, J. E. Brenman, J. A. Rafael, M. F. Peters, S. C. Froehner, E. P. Hoffman, J. S. Chamberlain, and D. S. Bredt. "Selective loss of sarcolemmal nitric oxide synthase in Becker muscular dystrophy." Journal of Experimental Medicine 184, no. 2 (August 1, 1996): 609–18. http://dx.doi.org/10.1084/jem.184.2.609.

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Becker muscular dystrophy is an X-linked disease due to mutations of the dystrophin gene. We now show that neuronal-type nitric oxide synthase (nNOS), an identified enzyme in the dystrophin complex, is uniquely absent from skeletal muscle plasma membrane in many human Becker patients and in mouse models of dystrophinopathy. An NH2-terminal domain of nNOS directly interacts with alpha 1-syntrophin but not with other proteins in the dystrophin complex analyzed. However, nNOS does not associate with alpha 1-syntrophin on the sarcolemma in transgenic mdx mice expressing truncated dystrophin proteins. This suggests a ternary interaction of nNOS, alpha 1-syntrophin, and the central domain of dystrophin in vivo, a conclusion supported by developmental studies in muscle. These data indicate that proper assembly of the dystrophin complex is dependent upon the structure of the central rodlike domain and have implications for the design of dystrophin-containing vectors for gene therapy.

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Patel, K., S. Leevers, S. Abbs, K. A. Hart, J. Z. Heckmatt, M. Bobrow, and V. Dubowitz. "ABSENCE OF DYSTROPHIN IN BECKER MUSCULAR DYSTROPHY." Lancet 333, no. 8628 (January 1989): 47. http://dx.doi.org/10.1016/s0140-6736(89)91705-4.

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HIGUCHI, Itsuro, Takahito NIIYAMA, Hidetoshi FUKUNAGA, Koichiro NAKAMURA, Masanori NAKAGAWA, and Mitsuhiro OSAME. "Dystrophin-Related Protein in Becker Muscular Dystrophy." Internal Medicine 33, no. 6 (1994): 334–36. http://dx.doi.org/10.2169/internalmedicine.33.334.

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Hoffman, Eric P., and Louis M. Kunkel. "Dystrophin abnormalities in Duchenne/Becker muscular dystrophy." Neuron 2, no. 1 (January 1989): 1019–29. http://dx.doi.org/10.1016/0896-6273(89)90226-2.

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Werneck, Lineu Cesar, and Eduardo Bonilla. "Immunohistochemical alterations of dystrophin in congenital muscular dystrophy." Arquivos de Neuro-Psiquiatria 53, no. 3a (September 1995): 416–23. http://dx.doi.org/10.1590/s0004-282x1995000300008.

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The dystrophin distribution in the plasma muscle membrane using immunohystochemistry was studied in 22 children with congenital muscular dystrophy. The dystrophin was detected by immunofluorescence in muscle biopsy through a polyclonal antibody. All the cases had patchy interruptions of the fluorescence in the plasma membrane. A large patchy interruption of the sarcolemma was found in 17 cases, small interruption in 12, and a combination of large and small patchy discontinuity in 7. Small gaps around the fiber like a rosary were found in 15 cases. The frequency of these abnormalities ranged cases from: all fibers in 5 cases, frequent in 8, occasional in 5, and rare in 4. Five cases had total absence of immunofluorescence. These results suggest that the dystrophin expression is abnormal in this group of children and that this type of abnormalities can not be differentiated from early Becker muscular dystrophy nor childhood autosomal recessive muscular dystrophy through immunohystochemistry alone.

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Mirabella, M., G. Galluzzi, G. Manfredi, E. Bertini, E. Ricci, R. De Leo, P. Tonali, and S. Servidei. "Giant dystrophin deletion associated with congenital cataract and mild muscular dystrophy." Neurology 51, no. 2 (August 1998): 592–95. http://dx.doi.org/10.1212/wnl.51.2.592.

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We report a patient with a large intragenic dystrophin deletion of exons 17-51 inclusive associated with congenital cataract and mild Becker muscular dystrophy. The cataract was similar to the congenital cataract described in the mdx mouse. The loss of 68% of the rod domain including hinge 2 and 3 regions did not adversely affect the correct localization of the dystrophin and the association with the dystrophin-associated glycoprotein complex. This observation may have implications for minigenes suitable for gene therapy.

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Hellebrekers, Danique M. J., Johan S. H. Vles, Sylvia Klinkenberg, and Jos G. M. Hendriksen. "The Neurocognitive and Behavioral Profiles of 3 Brothers With Becker Muscular Dystrophy." Child Neurology Open 7 (January 1, 2020): 2329048X2095721. http://dx.doi.org/10.1177/2329048x20957217.

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Becker muscular dystrophy patients generally carry in-frame mutations in the dystrophin gene, allowing the production of partially functional dystrophin protein. The presence of cognitive and behavioral comorbidities and the relation with the location of mutations has been scarcely investigated in Becker. This case report describes the neurocognitive and behavioral profiles of 3 brothers with Becker carrying an in-frame deletion of exons 45-48. The 3 cases underwent 2 consecutive neuropsychological assessments of which one assessment took place when they completed their primary education (age range of the cases: 11.2 -12.1 years). Intellectual abilities were normal to high and all cases had difficulties with processing speed and math. The brothers differed in intellectual abilities, executive functions, working memory, attention and reading abilities. Variability in cognitive development was noted as well. This report suggests that cognitive and behavioral functions in Becker vary regardless of gene mutation and exposer to similar environmental factors.

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Wilson, Kristin, Crystal Faelan, Janet C. Patterson-Kane, Daniel G. Rudmann, Steven A. Moore, Diane Frank, Jay Charleston, Jon Tinsley, G. David Young, and Anthony J. Milici. "Duchenne and Becker Muscular Dystrophies: A Review of Animal Models, Clinical End Points, and Biomarker Quantification." Toxicologic Pathology 45, no. 7 (October 2017): 961–76. http://dx.doi.org/10.1177/0192623317734823.

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Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are neuromuscular disorders that primarily affect boys due to an X-linked mutation in the DMD gene, resulting in reduced to near absence of dystrophin or expression of truncated forms of dystrophin. Some newer therapeutic interventions aim to increase sarcolemmal dystrophin expression, and accurate dystrophin quantification is critical for demonstrating pharmacodynamic relationships in preclinical studies and clinical trials. Current challenges with measuring dystrophin include the variation in protein expression within individual muscle fibers and across whole muscle samples, the presence of preexisting dystrophin-positive revertant fibers, and trace amounts of residual dystrophin. Immunofluorescence quantification of dystrophin can overcome many of these challenges, but manual quantification of protein expression may be complicated by variations in the collection of images, reproducible scoring of fluorescent intensity, and bias introduced by manual scoring of typically only a few high-power fields. This review highlights the pathology of DMD and BMD, discusses animal models of DMD and BMD, and describes dystrophin biomarker quantitation in DMD and BMD, with several image analysis approaches, including a new automated method that evaluates protein expression of individual muscle fibers.

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Istianah, Zakiah Nur, Sunartini Sunartini, and Sasmito Nugroho. "Motor clinical progression in a series of pediatric Duchenne and Becker muscular dystrophy cases." Paediatrica Indonesiana 59, no. 2 (March 13, 2019): 51–4. http://dx.doi.org/10.14238/pi59.2.2019.51-4.

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Muscular dystrophy is a neuromuscular disorder that begins with muscle weakness and impaired motor function. Duchenne muscular dystrophy (DMD) is more severe and destructive than Becker muscular dystrophy (BMD), and both are progressive in nature. These 2 types of muscular dystrophy are caused by mutations in related to X-chromosome genes.1 The mutations that occur in DMD are nonsense mutations. Deletion is present in 60% of DMD cases, while duplication occurs in 10% of DMD cases, resulting in loss of dystrophin protein. Mutations in BMD are missense mutations, so dystrophin is still formed, but in decreased amounts and quality.2,3 The prevalence of DMD was reported to be three times greater than that of BMD, with a prevalence of 1.02 per 10,000 male births vs. 0.36 per 10,000 male infants, respectiveley.4 Anatomical pathology examination revealed loss of dystrophin in the examination of muscle biopsy without the presence of evidence leading to other neuromuscular diseases. Clinical DMD symptoms begin to appear at the age of 2-4 years. The child is observed to fall often and has difficulty climbing stairs. Muscle weakness worsens, especially in the upper limbs, continuing with heart and respiratory problems. The main causes of death in DMD are respiratory failure and heart failure.5 The BMD has varied clinical symptoms, beginning with the appearance of myalgia, muscle cramps, and arm weakness progressing towards myopathy. Some patients are asymptomatic until the age of 15, but 50% of patients show symptoms at age 10, and almost all by age 20.6

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Chamova, T., V. Guergueltcheva, M. Raycheva, T. Todorov, J. Genova, S. Bichev, V. Bojinova, V. Mitev, I. Tournev, and A. Todorova. "Association Between Loss of Dp140 and Cognitive Impairment in Duchenne and Becker Dystrophies." Balkan Journal of Medical Genetics 16, no. 1 (June 1, 2013): 21–29. http://dx.doi.org/10.2478/bjmg-2013-0014.

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Abstract The presence of variable degrees of non progressive cognitive impairment is recognized as a clinical feature of patients with Duchenne and Becker muscular dystrophies (DMD and BMD), but its pathogenesis still remains a matter of debate. A number of findings have proved that rearrangements located in the second part of the dystrophin (DMD) gene seem to be preferentially associated with cognitive impairment. Dp140 is a distal dystrophin isoform, mainly expressed during fetal brain development, whose role for neuropsychological functioning was suggested. The aims of the current study were to explore the possible association between cognitive impairment and DNA mutations affecting the regulatory regions of Dp140, as well as to compare the neuropsychological functioning of patients affected with DMD and Intermediate muscular dystrophy (IMD) with those affected by Becker muscular dystrophy (BMD). Fiftythree patients genetically diagnosed with DMD, IMD and BMD, subdivided according to sites of mutations along the DMD gene, underwent a neuropsychological assessment, evaluating their general cognitive abilities, verbal memory, attention and executive functions. Twenty patients with mutations, terminating in exon 44 or starting at exon 45 were tested by polymerase chain reaction (PCR) amplification of microsatellites STR44, SK12, SK21 and P20 DXS269, in order to evaluate the integrity of the Dp140 promoter region. According to our statistical results, there was not a significant difference in terms of general intelligence between the allelic forms of the disease, a higher frequency of mental retardation was observed in DMD patients. The patients with BMD had better results on tests, measuring long-term verbal learning memory and executive functions. We found that patients lacking Dp140 performed more poorly on all neuropsychological tests compared to those with preserved Dp140. Overall, our findings suggest that the loss of Dp140 is associated with a higher risk of intellectual impairment among patients with dystrophinopathies and highlights the possible role of this distal isoform in normal cognitive development.

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Hori, Shinichiro, Sachiko Ohtani, Teruo Shimizu, Tohru Ibi, Ko Sahashi, Ikuya Nonaka, Kazuto Miyamoto, and Hitoshi Tanabe. "Multiplicity of abnormal dystrophin in Becker muscular dystrophy." Journal of the Neurological Sciences 121, no. 2 (February 1994): 183–89. http://dx.doi.org/10.1016/0022-510x(94)90350-6.

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Oliveira, Acary S. Bulle, Alberto A. Gabbai, Beny Schmidt, Beatriz Hitomi Kiyomoto, G. Camargo Lima, Carlo Minetti, and Eduardo Bonilla. "Carrier detection of duchenne and becker muscular dystrophy using muscle dystrophin immunohistochemistry." Arquivos de Neuro-Psiquiatria 50, no. 4 (December 1992): 478–85. http://dx.doi.org/10.1590/s0004-282x1992000400010.

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To ascertain whether dystrophin immunohistochemistry could improve DMD/ BMD carrier detection, we analyzed 14 muscle biopsies from 13 DMD and one BMD probable and possible carriers. All women were also evaluated using conventional methods, including genetic analysis, clinical and neurological evaluation, serum CK levels, KMG, and muscle biopsy. In 6 cases, there was a mosaic of dystrophin-positive and dystrophin-deficient fibers that allowed to make the diagnosis of a carrier state. Comparing dystrophin immunohistochemistry to the traditional methods, it was noted that this method is less sensitive than serum CK measuremens, but is more sensitive than EMG and muscle biopsy. The use of dystrophin immunohistochemistry in addition to CK, EMG and muscle biopsy improved the accuracy of carrier detection. This method is also helpful to distinguish manifesting DMD carriers from patients with other neuromuscular diseases like limb-girdle muscular dystrophy and spinal muscular atrophy.

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Harada, Yohei, Seth T. Sorensen, Akilandeswari Aravindhan, Vikki Stefans, and Aravindhan Veerapandiyan. "Dystrophinopathy in a Family Due to a Rare Nonsense Mutation Causing Predominant Behavioral Phenotype." Journal of Pediatric Neurology 18, no. 04 (September 30, 2019): 210–13. http://dx.doi.org/10.1055/s-0039-1698437.

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AbstractDystrophinopathies are a group of X-linked neuromuscular disorders resulting from mutations in DMD gene that encodes dystrophin. The clinical spectrum includes Duchenne muscular dystrophy, Becker muscular dystrophy, X-linked cardiomyopathy, and intellectual disability without involvement of skeletal muscle. Cognitive and behavioral problems are commonly seen among patients with dystrophinopathy. DMD gene is the largest human gene, consisting of 79 exons that produce dystrophin protein. Patients with genetic changes involving shorter dystrophin isoforms such as Dp140 and Dp71 are suggested to have higher rates of intellectual disability, attention-deficit/hyperactivity disorder, and other neuropsychiatric comorbidities. We describe three brothers who presented with prominent neurobehavioral deficits of varying degree, mild proximal weakness, and elevated serum creatine kinase due to a rare nonsense mutation, c.1702C > T; p.Gln568X, in exon 14 of DMD gene. Further studies are needed to better understand the effects of this rare mutation.

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Artilheiro, Mariana C., Cristina dos Santos Cardoso de Sá, Francis M. Fávero, Hanna C. Wutzki, Maria Bernadete Dutra de Resende, Fátima A. Caromano, and Mariana C. Voos. "Hand Function in Muscular Dystrophies." Perceptual and Motor Skills 124, no. 2 (January 16, 2017): 441–51. http://dx.doi.org/10.1177/0031512516688834.

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The aim of this study was to investigate the relationship between Performance of Upper Limb (PUL) and Jebsen–Taylor Test (JTT) to assess and monitor upper limb function progression in patients with muscular dystrophy. Thirty patients diagnosed with Duchenne muscular dystrophy, limb-girdle muscular dystrophy, Becker muscular dystrophy, myotonic dystrophy Type 1, and fascioscapulohumeral dystrophy were submitted to the shoulder, elbow, and wrist domains of PUL, and to JTT subtests. Spearman tests investigated the relationships between PUL and JTT total scores and domains. Correlations were classified as strong ( r ≥ 0.70), moderate (0.40 ≤ r < 0.70), or weak ( r ≤ 0.40). There were strong correlations between the PUL and JTT total scores ( r = −0.706). Although JTT measures time and PUL provides kinesiologic scores, these measures were related. Therefore, muscle synergies, which control the compensatory movements and motor functions involving mainly shoulder, elbow, wrist, and finger movements, are related to timed performance in patients with muscular dystrophies.

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Angelini, Corrado, and Elena Pinzan. "Advances in imaging of brain abnormalities in neuromuscular disease." Therapeutic Advances in Neurological Disorders 12 (January 2019): 175628641984556. http://dx.doi.org/10.1177/1756286419845567.

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Brain atrophy, white matter abnormalities, and ventricular enlargement have been described in different neuromuscular diseases (NMDs). We aimed to provide a comprehensive overview of the substantial advancement of brain imaging in neuromuscular diseases by consulting the main libraries ( Pubmed, Scopus and Google Scholar) including the more common forms of muscular dystrophies such as dystrophinopathies, dystroglycanopathies, myotonic dystrophies, facioscapulohumeral dystrophy, limb-girdle muscular dystrophy, congenital myotonia, and congenital myopathies. A consistent, widespread cortical and subcortical involvement of grey and white matter was found. Abnormalities in the functional connectivity in brain networks and metabolic alterations were observed with positron emission tomography (PET) and single photon emission computed tomography (SPECT). Pathological brain changes with cognitive dysfunction seemed to be frequently associated in NMDs. In particular, in congenital muscular dystrophies (CMDs), skeletal muscular weakness, severe hypotonia, WM abnormalities, ventricular dilatation and abnormalities in cerebral gyration were observed. In dystroglycanopathy 2I subtype (LGMD2I), adult patients showed subcortical atrophy and a WM periventricular involvement, moderate ventriculomegaly, and enlargement of subarachnoid spaces. Correlations with clinical features have been observed with brain imaging characteristics and alterations were prominent in congenital or childhood onset cases. In myotonic dystrophy type 2 (DM2) symptoms seem to be less severe than in type 1 (DM1). In Duchenne and Becker muscular dystrophies (DMD, BMD) cortical atrophy is associated with minimal ventricular dilatation and WM abnormalities. Late-onset glycogenosis type II (GSD II) or Pompe infantile forms are characterized by delayed myelination. Only in a few cases of oculopharyngeal muscular dystrophy (OPMD) central nervous system involvement has been described and associated with executive functions impairment.

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Dwianingsih, Ery Kus, Meydita Fuzia Putri Insani, Linda Pratiwi, Irianiwati Widodo, and Rusdy Ghazali Malueka. "Clinicopathologic and molecular profiles of Duchenne and Becker muscular dystrophy." Paediatrica Indonesiana 59, no. 5 (September 24, 2019): 257–64. http://dx.doi.org/10.14238/pi59.5.2019.257-64.

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Background Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic X-linked recessive diseases caused by mutations in the dystrophin (DMD) gene. To our knowledge, molecular analysis to differentiate between DMD and BMD has never been performed in Indonesia. Objective To elaborate the clinicopathologic and molecular profiles of DMD/BMD patients in Yogyakarta, Indonesia. Methods Eighteen muscle biopsy specimens of patients clinically suspected to have DMD/BMD were collected. Possible associations of clinical manifestations, histopathological grading, and immunohistochemistry (IHC) results were analyzed. Polymerase chain reaction (PCR) was performed to identify mutations in exon 52. Results. Positive Gower’s sign and high serum creatine kinase (CK) were observed in most patients. The IHC of dystrophin in two female patients suggested that they were manifesting carriers. Of the 16 male patients, 12 showed negative IHC staining, indicating DMD, while 4 patients demonstrated weak expression of dystrophin, indicating BMD. There was a significant association between high CK level and IHC results (P=0.005), indicating higher CK level in DMD patients. Histopathological grading of muscle biopsy was significantly associated with diagnosis of DMD/BMD using IHC (P=0.01), showing more severe tissue damage in DMD patients. None of the subjects had the single exon 52 deletion. Conclusion This is the first report of a clinicopathologic and molecular profile of DMD/BMD in an Indonesian population. Serum CK level and histopathological grading of muscle biopsy are useful in distinguishing DMD from BMD in settings where an IHC assay is not available.

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Tachi, Nobutada, Shuji Wakai, Yukie Watanabe, Kazuhiro Ohya, and Shunzo Chiba. "Asymptomatic Becker muscular dystrophy: Expression of dystrophin and dystrophin-related protein." Pediatric Neurology 9, no. 3 (May 1993): 207–9. http://dx.doi.org/10.1016/0887-8994(93)90086-r.

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Sheikh, Omar, and Toshifumi Yokota. "Advances in Genetic Characterization and Genotype–Phenotype Correlation of Duchenne and Becker Muscular Dystrophy in the Personalized Medicine Era." Journal of Personalized Medicine 10, no. 3 (September 3, 2020): 111. http://dx.doi.org/10.3390/jpm10030111.

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Currently, Duchenne muscular dystrophy (DMD) and the related condition Becker muscular dystrophy (BMD) can be usually diagnosed using physical examination and genetic testing. While BMD features partially functional dystrophin protein due to in-frame mutations, DMD largely features no dystrophin production because of out-of-frame mutations. However, BMD can feature a range of phenotypes from mild to borderline DMD, indicating a complex genotype–phenotype relationship. Despite two mutational hot spots in dystrophin, mutations can arise across the gene. The use of multiplex ligation amplification (MLPA) can easily assess the copy number of all exons, while next-generation sequencing (NGS) can uncover novel or confirm hard-to-detect mutations. Exon-skipping therapy, which targets specific regions of the dystrophin gene based on a patient’s mutation, is an especially prominent example of personalized medicine for DMD. To maximize the benefit of exon-skipping therapies, accurate genetic diagnosis and characterization including genotype–phenotype correlation studies are becoming increasingly important. In this article, we present the recent progress in the collection of mutational data and optimization of exon-skipping therapy for DMD/BMD.

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Agarwal, Rachna, Sujata Chaturvedi, Neelam Chhillar, Ishita Pant, and Anuradha Sharma. "Duchenne muscular dystrophy: A immunohistochemical profile and deletion pattern in dystrophin gene in North Indian population." Asian Journal of Medical Sciences 8, no. 6 (November 1, 2017): 13–18. http://dx.doi.org/10.3126/ajms.v8i6.18281.

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Background: Duchenne muscular dystrophy (DMD), one of the most common X linked muscular disorder, affecting 1 in 3500 male births and is caused by mutation in dystrophin gene. 65% of DMD cases are caused by large deletion of dystrophin gene, followed by duplication (5-10%) or point mutation (25-30%). There is wide mutation spectrum of the mutations in dystrophin gene. Hence, population specific information is needed on mutation spectrum and frequency of common mutations occurring in that particular population for appropriate counseling, prenatal diagnosis and for developing genetic therapy in future. Aims and Objectives: To find out the frequency and distribution of deletion in dystrophin gene in DMD patients along with contribution of pathology and genetic testing in diagnosis of DMD and Becker muscular dystrophy (BMD) in North Indian population.Materials and Methods: Dystrophin gene was screened for deletion by multiplex polymerase chain reaction (PCR). Out of 41 patients, 09 patients underwent muscle biopsy, on which immunohistochemistry was performed for dystrophin, sarcoglycan, dysferlin and merosin.Results: Majority of the deletions were located in distal hotspot region (26/39 ~66.66%) which includes the exons 45-55 and 15.38% of deletions were located at the proximal hotspot region (2- 19 exons).Conclusion: In the present study, 34% patients only showed deletion. Hence complete work up of any muscular dystrophy requires immnohistochemical analysis to see the expression of muscle proteins along with multipleplex PCR test to detect any exon deletion, multiplex ligation-dependent probe amplification (MLPA) to detect point mutation and duplication and western blotting to quantify the dystrophin protein.Asian Journal of Medical Sciences Vol.8(6) 2017 13-18

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Gajendran, Nadesan. "The root cause of Duchenne muscular dystrophy is the lack of dystrophin in smooth muscle of blood vessels rather than in skeletal muscle per se." F1000Research 7 (August 20, 2018): 1321. http://dx.doi.org/10.12688/f1000research.15889.1.

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Background: The dystrophin protein is part of the dystrophin associated protein complex (DAPC) linking the intracellular actin cytoskeleton to the extracellular matrix. Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy (D/BMD). Neuronal nitric oxide synthase associates with dystrophin in the DAPC to generate the vasodilator nitric oxide (NO). Systemic dystrophin deficiency, such as in D/BMD, results in muscle ischemia, injury and fatigue during exercise as dystrophin is lacking, affecting NO production and hence vasodilation. The role of neuregulin 1 (NRG) signaling through the epidermal growth factor family of receptors ERBB2 and ERBB4 in skeletal muscle has been controversial, but it was shown to phosphorylate α-dystrobrevin 1 (α-DB1), a component of the DAPC. The aim of this investigation was to determine whether NRG signaling had a functional role in muscular dystrophy. Methods: Primary myoblasts (muscle cells) were isolated from conditional knock-out mice containing lox P flanked ERBB2 and ERBB4 receptors, immortalized and exposed to CRE recombinase to obtain Erbb2/4 double knock-out (dKO) myoblasts where NRG signaling would be eliminated. Myotubes, the in vitro equivalent of muscle fibers, formed by fusion of the lox P flanked Erbb2/4 myoblasts as well as the Erbb2/4 dKO myoblasts were then used to identify changes in dystrophin expression. Results: Elimination of NRG signaling resulted in the absence of dystrophin demonstrating that it is essential for dystrophin expression. However, unlike the DMD mouse model mdx, with systemic dystrophin deficiency, lack of dystrophin in skeletal muscles of Erbb2/4 dKO mice did not result in muscular dystrophy. In these mice, ERBB2/4, and thus dystrophin, is expressed in the smooth muscle of blood vessels allowing normal blood flow through vasodilation during exercise. Conclusions: Dystrophin deficiency in smooth muscle of blood vessels, rather than in skeletal muscle, is the main cause of disease progression in DMD.

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Gajendran, Nadesan. "The root cause of Duchenne muscular dystrophy is the lack of dystrophin in smooth muscle of blood vessels rather than in skeletal muscle per se." F1000Research 7 (December 4, 2018): 1321. http://dx.doi.org/10.12688/f1000research.15889.2.

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Background: The dystrophin protein is part of the dystrophin associated protein complex (DAPC) linking the intracellular actin cytoskeleton to the extracellular matrix. Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophy (D/BMD). Neuronal nitric oxide synthase associates with dystrophin in the DAPC to generate the vasodilator nitric oxide (NO). Systemic dystrophin deficiency, such as in D/BMD, results in muscle ischemia, injury and fatigue during exercise as dystrophin is lacking, affecting NO production and hence vasodilation. The role of neuregulin 1 (NRG) signaling through the epidermal growth factor family of receptors ERBB2 and ERBB4 in skeletal muscle has been controversial, but it was shown to phosphorylate α-dystrobrevin 1 (α-DB1), a component of the DAPC. The aim of this investigation was to determine whether NRG signaling had a functional role in muscular dystrophy. Methods: Primary myoblasts (muscle cells) were isolated from conditional knock-out mice containing lox P flanked ERBB2 and ERBB4 receptors, immortalized and exposed to Cre recombinase to obtain Erbb2/4 double knock-out (dKO) myoblasts where NRG signaling would be eliminated. Myotubes, the in vitro equivalent of muscle fibers, formed by fusion of the lox P flanked Erbb2/4 myoblasts as well as the Erbb2/4 dKO myoblasts were then used to identify changes in dystrophin expression. Results: Elimination of NRG signaling resulted in the absence of dystrophin demonstrating that it is essential for dystrophin expression. However, unlike the DMD mouse model mdx, with systemic dystrophin deficiency, lack of dystrophin in skeletal muscles of Erbb2/4 dKO mice did not result in muscular dystrophy. In these mice, ERBB2/4, and thus dystrophin, is still expressed in the smooth muscle of blood vessels allowing normal blood flow through vasodilation during exercise. Conclusions: Dystrophin deficiency in smooth muscle of blood vessels, rather than in skeletal muscle, is the main cause of disease progression in DMD.

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Hoffman, E. P., L. M. Kunkel, C. Angelini, A. Clarke, M. Johnson, and J. B. Harris. "Improved diagnosis of Becker muscular dystrophy by dystrophin testing." Neurology 39, no. 8 (August 1, 1989): 1011. http://dx.doi.org/10.1212/wnl.39.8.1011.

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Angelini, C., A. H. Beggs, E. P. Hoffman, M. Fanin, and L. M. Kunkel. "Enormous dystrophin in a patient with Becker muscular dystrophy." Neurology 40, no. 5 (May 1, 1990): 808. http://dx.doi.org/10.1212/wnl.40.5.808.

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Minetti, C., G. Cordone, F. Beltrame, M. Bado, and E. Bonilla. "Disorganization of dystrophin costameric lattice in Becker muscular dystrophy." Muscle & Nerve 21, no. 2 (February 1998): 211–16. http://dx.doi.org/10.1002/(sici)1097-4598(199802)21:2<211::aid-mus8>3.0.co;2-e.

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Slater, Clarke R., and Louise V. B. Nicholson. "Is dystrophin labelling always discontinuous in Becker muscular dystrophy?" Journal of the Neurological Sciences 101, no. 2 (February 1991): 187–92. http://dx.doi.org/10.1016/0022-510x(91)90044-8.

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Vainzof, Mariz, Maria Rita Passos-Bueno, Rita C. M. Pavanello, and Mayana Zatz. "Is dystrophin always altered in Becker muscular dystrophy patients?" Journal of the Neurological Sciences 131, no. 1 (July 1995): 99–104. http://dx.doi.org/10.1016/0022-510x(95)00104-a.

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Journal articles on the topic 'Dystrophie musculaire de Becker'

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