Diagnosis of becker muscular dystrophy: Results of Re‐analysis of DNA samples

Straathof, C.S.M.; Heusden, D. van; Ippel, P. F.; Post, Jan G.; Voermans, Nicol C.; Visser, Marjolein; Brusse, Esther; Bergen, J.C. van den; Kooi, Anneke J. van der; Verschuuren, Jan J.; Ginjaar, H.B.

doi:10.1002/mus.24691

Cited by 3 publications

(1 citation statement)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found only three instances, two of whom had a p.Arg1967* mutation in exon 41 [40]. We conclude that, with the exception of mutations that affect exonic splicing enhancers and that result in exon skipping [32,[41][42][43][44][45][46][47][48][49], there is no evidence for the location of nonsense mutation affecting the severity of disease. Furthermore, no correlation was found between the type of the premature stop codon generated (UGA, UAA or UAG) and age at loss of ambulation, indicating that ataluren treatment benefit is not affected by stop codon type.…”

Section: Discussionmentioning

confidence: 58%

Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

et al. 2020

View full text Add to dashboard Cite

Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype–phenotype/–ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan–Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p ≤ 0.05). There were no DMD genotype–phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.

show abstract

Section: Discussionmentioning

confidence: 58%

Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

et al. 2020

View full text Add to dashboard Cite

show abstract

Combinatorial therapeutic activation with heparin and AICAR stimulates additive effects on utrophin A expression in dystrophic muscles

Péladeau¹,

Ahmed²,

Amirouche³

et al. 2015

Hum. Mol. Genet.

View full text Add to dashboard Cite

Upregulation of utrophin A is an attractive therapeutic strategy for treating Duchenne muscular dystrophy (DMD). Over the years, several studies revealed that utrophin A is regulated by multiple transcriptional and post-transcriptional mechanisms, and that pharmacological modulation of these pathways stimulates utrophin A expression in dystrophic muscle. In particular, we recently showed that activation of p38 signaling causes an increase in the levels of utrophin A mRNAs and protein by decreasing the functional availability of the destabilizing RNA-binding protein called K-homology splicing regulatory protein, thereby resulting in increases in the stability of existing mRNAs. Here, we treated 6-week-old mdx mice for 4 weeks with the clinically used anticoagulant drug heparin known to activate p38 mitogen-activated protein kinase, and determined the impact of this pharmacological intervention on the dystrophic phenotype. Our results show that heparin treatment of mdx mice caused a significant ∼1.5- to 3-fold increase in utrophin A expression in diaphragm, extensor digitorum longus and tibialis anterior (TA) muscles. In agreement with these findings, heparin-treated diaphragm and TA muscle fibers showed an accumulation of utrophin A and β-dystroglycan along their sarcolemma and displayed improved morphology and structural integrity. Moreover, combinatorial drug treatment using both heparin and 5-amino-4-imidazolecarboxamide riboside (AICAR), the latter targeting 5' adenosine monophosphate-activated protein kinase and the transcriptional activation of utrophin A, caused an additive effect on utrophin A expression in dystrophic muscle. These findings establish that heparin is a relevant therapeutic agent for treating DMD, and illustrate that combinatorial treatment of heparin with AICAR may serve as an effective strategy to further increase utrophin A expression in dystrophic muscle via activation of distinct signaling pathways.

show abstract

Intramuscular Adipose Tissue in the Lumbar Paraspinal Muscles Does Not Correlate With Low Back Pain in Medical Students

Gloyeske,

Bakewell,

Woodbury

et al. 2024

Journal of Diagnostic Medical Sonography

View full text Add to dashboard Cite

Objective: The objective of the study is to identify any intergroup differences or statistically significant correlations between paraspinal intramuscular adipose tissue (IntraMAT) deposition and variables such as low back pain, gender, self-reported activity level, body mass index (BMI), age, and academic class-year, as measured by sonographic intensity analysis. This study is specific to a cohort of first- and second-year medical students. Materials and Methods: The right lumbar paraspinal muscles, at the level of the fifth lumbar vertebrae, were investigated with sonography among a cohort of medical students. Image pixels, within the selected region of interest, were segregated by pixel intensity and analyzed for IntraMAT content. Participants reported on additional study variables by responding to a survey. The cohort responses were analyzed to seek correlations between those variables and IntraMAT. Results: The female participants were found to have more IntraMAT ( P < .001). Most participants reported low back pain. There were no significant correlations between IntraMAT and reported low back pain, academic class year, or BMI. Moderate exercise increased IntraMAT deposition, and each year of increasing age decreased IntraMAT ( P < .05). Second-year students experienced more self-reported low back pain than first-year students. Conclusion: A cohort of medical students who were reportedly sedentary had more low back pain than their peers. Back pain was more prevalent in second-year students, irrespective of age, suggesting that ill effects of a sedentary lifestyle may be cumulative. The validity of the sonographic pixel intensity analysis performed was supported by the highly significant increase in IntraMAT observed in female participants. The relationship between low back pain, exercise, BMI, and IntraMAT was uncertain based on available evidence and the results of this study.

show abstract

Diagnosis of becker muscular dystrophy: Results of Re‐analysis of DNA samples

Abstract: Refining DNA analysis in previously undiagnosed cases can identify mutations in the DMD gene and provide genetic diagnosis of BMD. A delayed diagnosis can still be valuable for the proband or the relatives of BMD patients.

Cited by 3 publications

References 22 publications

Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study

Combinatorial therapeutic activation with heparin and AICAR stimulates additive effects on utrophin A expression in dystrophic muscles

Intramuscular Adipose Tissue in the Lumbar Paraspinal Muscles Does Not Correlate With Low Back Pain in Medical Students

Contact Info

Product

Resources

About