scholarly journals Lower Extremity Muscle Involvement in the Intermediate and Bethlem Myopathy Forms of COL6-Related Dystrophy and Duchenne Muscular Dystrophy: A Cross-Sectional Study

2020 ◽  
Vol 7 (4) ◽  
pp. 407-417
Author(s):  
Abhinandan Batra ◽  
Donovan J. Lott ◽  
Rebecca Willcocks ◽  
Sean C. Forbes ◽  
William Triplett ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Matrix Protein ◽  
Fatty Infiltration ◽  
Extracellular Matrix Protein ◽  
Collagen Vi ◽  
Muscle Involvement ◽  
Lower Extremity Muscle ◽  
Unaffected Control

Collagen VI-related dystrophies (COL6-RDs) and Duchenne muscular dystrophy (DMD) cause progressive muscle weakness and disability. COL6-RDs are caused by mutations in the COL6 genes (COL6A1, COL6A2 and COL6A3) encoding the extracellular matrix protein collagen VI, and DMD is caused by mutations in the DMD gene encoding the cytoplasmic protein dystrophin. Both COL6-RDs and DMD are characterized by infiltration of the muscles by fatty and fibrotic tissue. This study examined the effect of disease pathology on skeletal muscles in lower extremity muscles of COL6-RDs using timed functional tests, strength measures and qualitative/ quantitative magnetic resonance imaging/spectroscopy measures (MRI/MRS) in comparison to unaffected (control) individuals. Patients with COL6-RD were also compared to age and gender matched patients with DMD. Patients with COL6-RD presented with a typical pattern of fatty infiltration of the muscle giving rise to an apparent halo effect around the muscle, while patients with DMD had evidence of fatty infiltration throughout the muscle areas imaged. Quantitatively, fat fraction, and transverse relaxation time (T2) were elevated in both COL6-RD and DMD patients compared to unaffected (control) individuals. Patients with COL6-RD had widespread muscle atrophy, likely contributing to weakness. In contrast, patients with DMD revealed force deficits even in muscle groups with increased contractile areas.

scholarly journals MR biomarkers predict clinical function in Duchenne muscular dystrophy

Neurology ◽  
2020 ◽  
Vol 94 (9) ◽  
pp. e897-e909 ◽  
Author(s):  
Alison M. Barnard ◽  
Rebecca J. Willcocks ◽  
William T. Triplett ◽  
Sean C. Forbes ◽  
Michael J. Daniels ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Vastus Lateralis ◽  
Strong Relationship ◽  
Biceps Femoris ◽  
Loss Of Function ◽  
Long Head ◽  
Biceps Femoris Long Head ◽  
Over Time

ObjectiveTo investigate the potential of lower extremity magnetic resonance (MR) biomarkers to serve as endpoints in clinical trials of therapeutics for Duchenne muscular dystrophy (DMD) by characterizing the longitudinal progression of MR biomarkers over 48 months and assessing their relationship to changes in ambulatory clinical function.MethodsOne hundred sixty participants with DMD were enrolled in this longitudinal, natural history study and underwent MR data acquisition of the lower extremity muscles to determine muscle fat fraction (FF) and MRI T2 biomarkers of disease progression. In addition, 4 tests of ambulatory function were performed. Participants returned for follow-up data collection at 12, 24, 36, and 48 months.ResultsLongitudinal analysis of the MR biomarkers revealed that vastus lateralis FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 biomarkers were the fastest progressing biomarkers over time in this primarily ambulatory cohort. Biomarker values tended to demonstrate a nonlinear, sigmoidal trajectory over time. The lower extremity biomarkers predicted functional performance 12 and 24 months later, and the magnitude of change in an MR biomarker over time was related to the magnitude of change in function. Vastus lateralis FF, soleus FF, vastus lateralis MRI T2, and biceps femoris long head MRI T2 were the strongest predictors of future loss of function, including loss of ambulation.ConclusionsThis study supports the strong relationship between lower extremity MR biomarkers and measures of clinical function, as well as the ability of MR biomarkers, particularly those from proximal muscles, to predict future ambulatory function and important clinical milestones.ClinicalTrials.gov identifierNCT01484678.

Assessment of muscle involvement in patients with Duchenne muscular dystrophy via segmental multifrequency bioelectrical analysis

2019 ◽  
Vol 29 (9) ◽  
pp. 671-677
Author(s):  
Satoshi Kuru ◽  
Tomoka Uchiyama ◽  
Ayako Hattori ◽  
Takatoshi Sato ◽  
Terumi Murakami ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Involvement

scholarly journals Structure and binding properties of collagen type XIV isolated from human placenta.

1993 ◽  
Vol 120 (2) ◽  
pp. 557-567 ◽  
Author(s):  
J C Brown ◽  
K Mann ◽  
H Wiedemann ◽  
R Timpl
Keyword(s):  
Human Placenta ◽  
Matrix Protein ◽  
Cell Attachment ◽  
Chondroitin Sulphate ◽  
Heparan Sulphate ◽  
Extracellular Matrix Protein ◽  
Neutral Salt ◽  
Heparin Binding ◽  
Collagen Vi ◽  
Sulphate Proteoglycan

Collagen XIV was isolated from neutral salt extracts of human placenta and purified by several chromatographic steps including affinity binding to heparin. The same procedures also led to the purification of a tissue form of fibronectin. Collagen XIV was demonstrated by partial sequence analysis of its Col1 and Col2 domains and by electron microscopy to be a disulphide-linked molecule with a characteristic cross-shape. The individual chains had a size of approximately 210 kD, which was reduced to approximately 180 kD (domain NC3) after treatment with bacterial collagenase. Specific antibodies mainly to NC3 epitopes were obtained by affinity chromatography and used in tissue and cell analyses by immunoblotting and radioimmunoassays. Two sequences from NC3 were identified on fragments obtained after trypsin cleavage. They were identical to cDNA-derived sequences of undulin, a noncollagenous extracellular matrix protein. This suggests that collagen XIV and undulin may be different splice variants from the same gene. Heparin binding was confirmed in ligand assays with a large basement membrane heparan sulphate proteoglycan. This binding could be inhibited by heparin and heparan sulphate but not by chondroitin sulphate. In addition, collagen XIV bound to the triple helical domain of collagen VI. The interactions with heparin sulphate proteoglycan and collagen VI were not shared by the NC3 domain, or by reduced and alkylated collagen XIV. No or only low binding was observed for collagens I-V, pN-collagens I and III, and several noncollagenous matrix proteins, including laminin, recombinant nidogen, BM-40/osteonectin, plasma and tissue fibronectin, vitronectin, and von Willebrand factor. Insignificant activity was also shown in cell attachment assays with nine established cell lines.

Lower Limb Flexibility in Children With Duchenne Muscular Dystrophy: Effects on Functional Performance

2019 ◽  
Vol 31 (1) ◽  
pp. 42-46
Author(s):  
Lütfiye Akkurt ◽  
İpek Alemdaroğlu Gürbüz ◽  
Ayşe Karaduman ◽  
Öznur Tunca Yilmaz
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Lower Extremity ◽  
Lower Limb ◽  
Functional Performance ◽  
Lower Limbs ◽  
Performance Tests ◽  
Gastrocnemius Muscles ◽  
Minute Walk ◽  
Walk Tests

Objective: To investigate the effects of lower limb flexibility on the functional performance of children with Duchenne muscular dystrophy. Methods: Thirty children, whose functional levels were at 1 or 2 according to the Brooke Lower Extremity Functional Classification Scale, were included in this study. The flexibilities of the hamstrings, hip flexors, tensor fascia latae, and gastrocnemius muscles were evaluated in the children’s dominant lower limbs. The children’s functional performance was assessed using 6-minute walk tests and timed performance tests. The correlations between the flexibilities of the lower limb muscles and the performance tests were examined. Results: The flexibilities of the lower extremity muscles were found to be correlated to the 6-minute walk tests and the timed performance tests. The flexibility of the hamstrings (r = −.825), the gastrocnemius muscles (r = .545), the hip flexors (r = .481), and the tensor fascia latae (r = .445) were found to be correlated with functional performance as measured by the 6-minute walk tests (P < .05). Discussion: The results of the current study indicate that the flexibility of the lower limbs has an effect on functional performance in the early stages of Duchenne muscular dystrophy. More research is needed to determine the functional effects of flexibility on performance by adding long-term flexibility exercises to the physiotherapy programs of children with Duchenne muscular dystrophy.

Phosphorylation of the carboxyl-terminal region of dystrophin

1996 ◽  
Vol 74 (4) ◽  
pp. 431-437 ◽  
Author(s):  
Marek Michalak ◽  
Susan Y. Fu ◽  
Rachel E. Milner ◽  
Jody L. Busaan ◽  
Jacqueline E. Hance
Keyword(s):  
Extracellular Matrix ◽  
Muscular Dystrophy ◽  
Protein Kinases ◽  
Protein Interactions ◽  
Matrix Protein ◽  
Casein Kinase ◽  
Terminal Region ◽  
Extracellular Matrix Protein

Dystrophin is a protein product of the gene responsible for Duchenne and Becker muscular dystrophy. The protein is localized to the inner surface of sarcolemma and is associated with a group of membrane (glyco)proteins. Dystrophin links cytoskeletal actins via the dystrophin-associated protein complex to extracellular matrix protein, laminin. This structural organization implicates the role of dystrophin in stabilizing the sarcolemma of muscle fibers. Precisely how dystrophin functions is far from clear. The presence of an array of isoforms of the C-terminal region of dystrophin suggests that dystrophin may have functions other than structural. In agreement, many potential phosphorylation sites are found in the C-terminal region of dystrophin, and the C-terminal region of dystrophin is phosphorylated both in vitro and in vivo by many protein kinases, including MAP kinase, p34cdc2 kinase, CaM kinase, and casein kinase, and is dephosphorylated by calcineurin. The C-terminal domain of dystrophin is also a substrate for hierarchical phosporylation by casein kinase-2 and GSK-3. These observations, in accordance with the finding that the cysteine-rich region binds to Ca2+, Zn2+, and calmodulin, suggest an active involvement of dystrophin in transducing signals across muscle sarcolemma. Phosphorylation–dephosphorylation of the C-terminal region of dystrophin may play a role in regulating dystrophin–protein interactions and (or) transducing signal from the extracellular matrix via the dystrophin molecule to the cytoskeleton.Key words: Duchenne muscular dystrophy, protein phosphorylation, protein kinases, calcineurin, cytoskeleton.

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