Abstract
Limb-girdle muscular dystrophy type 2B and the distal muscular dystrophy of Miyoshi (MM) are caused by mutations in the DYSF gene encoding the protein dysferlin. Although the clinical features of LGMD2B and MM are different, both phenotypes can be detected among patients belonging to the same family. The clinical heterogeneity might be attributed to additional epigenetic factors. Dysferlin immunolocalizes to the sarcolemma and has a central role in membrane fusion and repair of the plasmalemma lesions generated by eccentric muscle contraction, as demonstrated by the presence of many crowded vesicles just beneath the sarcolemma. Several studies have reported a prominent inflammatory response in muscle with dysferlinopathy and increased ubiquitin-proteasomal and autophagic degradation in part secondary to high levels of regeneration and inflammation. The detection of dysferlin deficiency in muscle offers an important diagnostic tool, which has allowed the molecular diagnosis of dysferlinopathy in most patients.
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Angelini, C. (2018). Limb-Girdle Muscular Dystrophy Type 2B. In: Genetic Neuromuscular Disorders. Springer, Cham. https://doi.org/10.1007/978-3-319-56454-8_12
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DOI: https://doi.org/10.1007/978-3-319-56454-8_12
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