Objective: Becker muscular dystrophy (BMD) is characterised by broad clinical variability. Ongoing studies exploring dystrophin restoration in Duchenne muscular dystrophy ask for better understanding of the relation between dystrophin levels and disease severity. We studied this relation in BMD patients with varying mutations, including a large subset with an exon 45-47 deletion.
Methods: Dystrophin was quantified by western blot analyses in a fresh muscle biopsy of the anterior tibial muscle. Disease severity was assessed using quantitative muscle strength measurements and functional disability scoring. MRI of the leg was performed in a subgroup to detect fatty infiltration.
Results: 33 BMD patients participated. No linear relation was found between dystrophin levels (range 3%-78%) and muscle strength or age at different disease milestones, in both the whole group and the subgroup of exon 45-47 deleted patients. However, patients with less than 10% dystrophin all showed a severe disease course. No relation was found between disease severity and age when analysing the whole group. By contrast, in the exon 45-47 deleted subgroup, muscle strength and levels of fatty infiltration were significantly correlated with patients' age.
Conclusions: Our study shows that dystrophin levels appear not to be a major determinant of disease severity in BMD, as long as it is above approximately 10%. A significant relation between age and disease course was only found in the exon 45-47 deletion subgroup. This suggests that at higher dystrophin levels, the disease course depends more on the mutation site than on the amount of the dystrophin protein produced.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1136/jnnp-2013-306350 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of 2-Aminoethoxydiphenyl Borate on the State of Skeletal Muscles in Dystrophin-Deficient Mice.
Front Biosci (Landmark Ed)
December 2024
Department of Biochemistry, Cell Biology and Microbiology, Mari State University, 424001 Yoshkar-Ola, Russia.
Objective: Ca overload of muscle fibers is one of the factors that secondarily aggravate the development of Duchenne muscular dystrophy (DMD). The purpose of this study is to evaluate the effects of the Ca channel modulator 2-aminoethoxydiphenyl borate (APB) on skeletal muscle pathology in dystrophin-deficient mice.
Methods: Mice were randomly divided into six groups: wild type (WT), WT+3 mg/kg APB, WT+10 mg/kg APB, , +3 mg/kg APB, +10 mg/kg APB.
A New Perspective on Drugs for Duchenne Muscular Dystrophy: Proposals for Better Respiratory Outcomes and Improved Regulatory Pathways.
Paediatr Drugs
December 2024
Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
New drugs for Duchenne muscular dystrophy (DMD) are emerging rapidly. However, we and others believe these drugs are achieving regulatory approval prematurely. It is the cardiorespiratory complications of DMD that cause the disease's major morbidities and that determine survival.
View Article and Find Full Text PDFThe role of dystrophin isoforms and interactors in the brain.
Brain
December 2024
Dubowitz Neuromuscular Centre, University College London, Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
Dystrophin is a protein crucial for maintaining the structural integrity of skeletal muscle. So far, the attention was focused on the role of dystrophin in muscle in view of the devastating progression of weakness and early death that characterises Duchenne muscular dystrophy. However, in the last few years, the role of shorter dystrophin isoforms, including development and adult expression-specific mechanisms, has been a greater focus.
View Article and Find Full Text PDFMethylphenidate treatment of a Chinese boy with Becker muscular dystrophy combined with attention deficit hyperactivity disorder: a case report.
Front Neurosci
November 2024
Department of Pediatrics, West China Second University Hospital, Sichuan University, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education (MOE), Chengdu, Sichuan, China.
Background: Becker muscular dystrophy (BMD) is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis, caused by mutations in the DMD gene, which encodes dystrophin protein. Different from Duchenne Muscular Dystrophy (DMD), in which dystrophin is completely absent in muscle tissue, while in BMD, the dystrophin gene can express some protein, but not enough. It has also been shown that a proportion of patients with DMD suffer from attention deficit hyperactivity disorder (ADHD), and the use of the stimulant methylphenidate has been suggested for the treatment of patients with DMD in combination with ADHD.
View Article and Find Full Text PDFIdentification of reference microRNAs in skeletal muscle of a canine model of Duchenne muscular dystrophy.
Wellcome Open Res
November 2024
Department of Clinical Science and Services, Comparative Neuromuscular Diseases Laboratory, Royal Veterinary College, London, NW1 0TU, UK.
Article Synopsis
- Duchenne muscular dystrophy (DMD) is a severe condition resulting from mutations in the dystrophin gene, and DE50-MD dogs serve as a model to test new therapies for this disease.
- * Researchers aimed to find stable microRNA (miR) references for normalizing expression data across different ages and muscle groups in both healthy (WT) and DMD-affected dogs.
- * The study identified four stable miRs (miR-191, let-7b, miR-125a, and miR-15a) that can be used to accurately normalize the expression levels of other miRs in muscle, indicating differences in miR levels between DE50-MD and WT dogs.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!