Related Experiment Video
Updated: Jul 7, 2026
06:35
Cell Membrane Repair Assay Using a Two-photon Laser Microscope
Published on: January 2, 2018
Dysferlin-deficient muscular dystrophy features amyloidosis
Simone Spuler1, Miriam Carl, Joanna Zabojszcza
1Muscle Research Unit, Experimental and Clinical Research Center at the Charité and the Max-Delbrück Center, Berlin, Germany. simone.spuler@charite.de
Annals of Neurology
|February 29, 2008
Summary
Mutations in the dysferlin (DYSF) gene can lead to muscular dystrophy and amyloid deposits. This study identifies DYSF mutations as a cause of amyloidosis in limb girdle muscular dystrophy type 2B.
Area of Science:
- Neurology
- Genetics
- Biochemistry
Background:
- Dysferlin (DYSF) gene mutations are linked to limb girdle muscular dystrophy type 2B and Miyoshi's myopathy.
- The structural impact of DYSF mutations on protein function remains unclear.
Purpose of the Study:
- To investigate the consequences of DYSF mutations on protein structure.
- To identify the underlying genetic cause of dysferlin-deficient muscular dystrophy in affected families.
Main Methods:
- Sequencing of the dysferlin gene in patients.
- Analysis of muscle biopsy specimens using histochemistry, immunohistochemistry, and electron microscopy.
- Development of antibodies against N-terminal dysferlin peptides.
Main Results:
- Three families presented with muscular dystrophy due to homozygous or compound heterozygous DYSF mutations.
- Amyloid deposits were observed in both sarcolemmal and interstitial tissues.
- Identified DYSF mutations were localized to the N-terminal region of the protein.
- Dysferlin was confirmed as a component of the amyloid deposits.
Conclusions:
- Limb girdle muscular dystrophy type 2B is the first muscular dystrophy associated with amyloidosis.
- Future molecular treatment strategies must address the role of amyloidogenesis in DYSF-related muscular dystrophies.
Related Concept Videos
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
01:21Satellite Stem Cells and Muscular Dystrophy
Satellite stem cells or myosatellite cells are quiescent stem cells that Alexander Mauro first identified in 1961. These cells are located between the sarcolemma, the plasma membrane of muscle fibers, and the basal lamina, the connective tissue sheath covering it. These mononucleated cells are activated in response to muscle injury, can transform into myoblasts, and may form or repair muscle fibers. Myosatellite cells can provide additional myonuclei for muscle regeneration or return to a...
01:28Disorders of the Skeletal Muscle
The clinical conditions affecting the skeletal muscle tissue are broadly categorized as musculoskeletal and neuromuscular disorders.
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
Musculoskeletal disorders
Musculoskeletal disorders involve injuries and conditions affecting the skeletal muscles and associated connective tissues. These disorders can arise from acute biomechanical stresses or chronic overuse and can occur across different age groups. Common injuries include sprains, fractures, and muscular strains, often resulting from...
01:26Cross-bridge Cycle
As muscle contracts, the overlap between the thin and thick filaments increases, decreasing the length of the sarcomere—the contractile unit of the muscle—using energy in the form of ATP. At the molecular level, this is a cyclic, multistep process that involves binding and hydrolysis of ATP, and movement of actin by myosin.
01:22Myasthenia Gravis ll: Pathophysiology
The disease process of myasthenia gravis begins at the neuromuscular junction, where antibodies attack key proteins needed for muscle activation. This immune reaction weakens signal transmission, leading to the characteristic muscle fatigue and weakness that define the condition.Immune-Mediated DamageIn most individuals, antibodies target acetylcholine receptors (AChRs) on the postsynaptic membrane of muscle cells. By blocking acetylcholine binding, these antibodies prevent the nerve signal...