Clinical Approach to the Diagnostic Evaluation of Hereditary and Acquired Neuromuscular Diseases

McDonald, Craig M.

doi:10.1016/j.pmr.2012.06.011

Cited by 95 publications

(65 citation statements)

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“…A majority of the most commonly disrupted genes in muscle disease are poorly expressed in blood and fibroblasts, suggesting that RNA-seq from these easily accessible tissues may be underpowered to detect relevant transcriptional aberrations in certain genes. For these reasons, we chose to pursue RNA-seq from primary muscletissue biopsies, which are routinely performed as part of the diagnostic evaluation of undiagnosed muscle disease patients (21, 22). …”

Section: Resultsmentioning

confidence: 99%

Improving genetic diagnosis in Mendelian disease with transcriptome sequencing

et al. 2017

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Exome and whole-genome sequencing are becoming increasingly routine approaches in Mendelian disease diagnosis. Despite their success, the current diagnostic rate for genomic analyses across a variety of rare diseases is approximately 25 to 50%. We explore the utility of transcriptome sequencing [RNA sequencing (RNA-seq)] as a complementary diagnostic tool in a cohort of 50 patients with genetically undiagnosed rare muscle disorders. We describe an integrated approach to analyze patient muscle RNA-seq, leveraging an analysis framework focused on the detection of transcript-level changes that are unique to the patient compared to more than 180 control skeletal muscle samples. We demonstrate the power of RNA-seq to validate candidate splice-disrupting mutations and to identify splice-altering variants in both exonic and deep intronic regions, yielding an overall diagnosis rate of 35%. We also report the discovery of a highly recurrent de novo intronic mutation in COL6A1 that results in a dominantly acting splice-gain event, disrupting the critical glycine repeat motif of the triple helical domain. We identify this pathogenic variant in a total of 27 genetically unsolved patients in an external collagen VI–like dystrophy cohort, thus explaining approximately 25% of patients clinically suggestive of having collagen VI dystrophy in whom prior genetic analysis is negative. Overall, this study represents a large systematic application of transcriptome sequencing to rare disease diagnosis and highlights its utility for the detection and interpretation of variants missed by current standard diagnostic approaches.

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Section: Resultsmentioning

confidence: 99%

Improving genetic diagnosis in Mendelian disease with transcriptome sequencing

et al. 2017

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“…Signs of myopathy may be detected from birth through laboratory findings although the clinical sign usually occurs later between two and three years of age (Gardner-Medwin, 1980;McDonald, 2012). Creatine kinase (CK) blood levels are often utilized as diagnostic markers for DMD (Cacchiarelli, 2011).…”

Section: Introductionmentioning

confidence: 99%

Whole-Body Vibration Exercise Is Well Tolerated in Patients With Duchenne Muscular Dystrophy: A Systematic Review

Moreira-Marconi¹,

Sá-Caputo²,

Dionello³

et al. 2017

Afr J Tradit Complement Altern Med

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Background:Duchenne muscular dystrophy (DMD) is caused by a defective gene located on the X-chromosome, responsible for the production of the dystrophin protein. Complications in the musculoskeletal system have been previously described in DMD patients. Whole body vibration exercise (WBVE) is a treatment that improves musculoskeletal function in movement disorders. The aim of this study was to review the effects of WBVE on functional mobility, bone and muscle in DMD patients.Materials and Methods:Four databases were searched. Three eligible studies were found; all three conclude the management of DMD patients with WBV was clinically well tolerated. The studies used a side-alternating WBV system, frequencies 7 - 24 Hz; and amplitudes 2 - 4 mm.Results:A work indicates that a temporary increase in creatine kinase in DMD during the first days of WBV was observed, but other authors did not find changes. No significant changes in bone mass, muscle strength or bone markers. Some patients reported subjective functional improvement during training. Interpretation:Conclusion:It is concluded that WBV seems to be a feasible and well tolerated exercise modality in DMD patients.

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“…Neuropathies. 51,52 Pathophysiology of respiratory failure in NMD Children with progressive NMD undergo a typical evolution of respiratory impairment. Weakness that involves respiratory muscles, which includes the diaphragm, chest wall, and bulbar control, can lead to the inability to take deep breaths and to clear secretions effectively from the airways.…”

Section: Myopathies; (Ii) Central Nervous System Disorders; and (Iii)mentioning

confidence: 99%