PCR and immunoblot analyses of dystrophin in Becker muscular dystrophy

Uchino, Makoto; Miike, Teruhisa; Iwashita, Hiroshi; Uyama, Eiichiro; Yoshioka, Ken; Sugino, Shigeto; Ando, Masayuki

doi:10.1016/0022-510x(94)90331-x

Cited by 4 publications

(3 citation statements)

References 14 publications

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“…20 Dystrophin is a main cytoskeletal structural protein [21][22][23][24][25][26][27][28] involved in skeletal and cardiac muscle cell mechanotransduction. 21,28 -30 Although dystrophin is present in vascular smooth muscle cells, 25,[31][32][33] no functional study in blood vessels has been performed, especially in response to mechanical stimuli such as pressure and flow, the main effectors of vascular tone and blood supply. [1][2][3][4][5][6][7][8] The possibility of a specific vascular malfunction, such as a decrease in local blood flow supply to end organs, has never been investigated in such dystrophin-related diseases as Duchenne dystrophy, although it might at least accelerate damage to tissues and especially damage to cardiac and skeletal muscles.…”

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confidence: 99%

Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin

et al. 2001

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Background-Dystrophin has a key role in striated muscle mechanotransduction of physical forces. Although cytoskeletal elements play a major role in the mechanotransduction of pressure and flow in vascular cells, the role of dystrophin in vascular function has not yet been investigated. Thus, we studied endothelial and muscular responses of arteries isolated from mice lacking dystrophin (mdx mice). Methods and Results-Carotid and mesenteric resistance arteries 120 m in diameter were isolated and mounted in vitro in an arteriograph to control intraluminal pressure and flow. Blood pressure was not affected by the absence of dystrophin. Pressure-induced (myogenic), phenylephrine-induced, and KCl-induced forms of tone were unchanged. Flow (shear stress)-induced dilation in arteries isolated from mdx mice was decreased by 50% to 60%, whereas dilation to acetylcholine or sodium nitroprusside was unaffected. NG-nitro-L-arginine methyl ester-sensitive flow dilation was also decreased in arteries from mdx mice. Thus, the absence of dystrophin was associated with a defect in signal transduction of shear stress. Dystrophin was present in vascular endothelial and smooth muscle cells, as shown by immunolocalization, and localized at the level of the plasma membrane, as seen by confocal microscopy of perfused isolated arteries. Conclusions-This

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confidence: 99%

Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin

et al. 2001

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“…The development of semiquantitative fluorescent multiplex PCR and the use of the CGH gene-specific array have allowed the detection of dupdels in carrier girls [ 148 ]. However, immunoblot analysis can identify abnormalities in dystrophin in the absence of detectable PCR deletions within the gene [ 149 ]. Although multiplex ligation-dependent probe amplification holds the power to detect 70% of Dystrophin gene intragenic dupdels [ 60 , 61 , 62 , 63 ], it is unable to detect nucleotide alterations (point mutations).…”

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confidence: 99%

Advances in Dystrophinopathy Diagnosis and Therapy

Saad,

Siciliano,

Angelini

2023

Biomolecules

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Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the Dystrophin gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the Dystrophin gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care.

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“…Becker muscular dystrophy (BMD) occurs due to a deletion, duplication, or point mutation in the dystrophin gene on chromosome Xp21.1, which leads to a reduced amount or abnormal size of the muscle dystrophin isoform (1)(2)(3). In typical BMD patients, the clinical course is more benign than in Duchenne muscular dystrophy.…”

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confidence: 99%

Life-threatening Arrhythmias in a Becker Muscular Dystrophy Family due to the Duplication of Exons 3-4 of the Dystrophin Gene

et al. 2015

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We herein present a report of three patients with Becker muscular dystrophy in the same family who developed complete atrioventricular block or ventricular tachycardia with severe cardiomyopathy. Our cases became unable to walk in their teens, and were introduced to mechanical ventilation due to respiratory muscle weakness in their twenties and thirties. In all three cases, a medical device such as a permanent cardiac pacemaker or an implantable cardiac defibrillator was considered to be necessary. The duplication of exons 3-4 in the dystrophin gene was detected in two of the patients. In patients with Becker muscular dystrophy, complete atrioventricular block or ventricular tachycardia within a family has rarely been reported. Thus attention should be paid to the possibility of severe arrhythmias in the severe phenotype of Becker muscular dystrophy.

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PCR and immunoblot analyses of dystrophin in Becker muscular dystrophy

Cited by 4 publications

References 14 publications

Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin

Flow (Shear Stress)–Induced Endothelium-Dependent Dilation Is Altered in Mice Lacking the Gene Encoding for Dystrophin

Advances in Dystrophinopathy Diagnosis and Therapy

Life-threatening Arrhythmias in a Becker Muscular Dystrophy Family due to the Duplication of Exons 3-4 of the Dystrophin Gene

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