In the absence of dysferlin, skeletal muscle cells fail to reseal properly after injury, resulting in slow progress of the dysferlinopathy muscular dystrophy (MD).
This approach has also been explored in several other genetic disorders, including laminin α2 chain-deficient congenital muscular dystrophy, dysferlin-deficient muscular dystrophy (e.g., Miyoshi myopathy and limb-girdle muscular dystrophy type 2B), sarcoglycanopathy (limb-girdle muscular dystrophy type 2C), and Fukuyama congenital muscular dystrophy.
Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair and underlies a recessive form of inherited muscular dystrophy.
These findings identify that mitochondrial deficit in muscular dystrophy compromises the repair of injured myofibers and show that this repair mechanism is distinct from and complimentary to the dysferlin-mediated repair of injured myofibers.
The phenotypic overlap of ANO5 myopathies with dysferlin-associated muscular dystrophies has inspired the hypothesis that ANO5, like dysferlin, may be involved in the repair of muscle membranes following injury.
Mutations in dysferlin, the first protein linked with the cell membrane repair mechanism, causes a group of muscular dystrophies called dysferlinopathies.
Recessive mutations in ANO5 cause primary skeletal muscle disorders (limb-girdle muscular dystrophy 2L and distal muscular dystrophy), which are phenotypically similar to dysferlinopathy, a muscular dystrophy due to dysferlin-encoding gene (DYSF) mutations.
Mutations in the dysferlin gene are involved in two autosomal recessive muscular dystrophies: Miyoshi myopathy and limb-girdle muscular dystrophy type 2B.
Recently, it was reported that a mutation in the dysferlin gene and/or dysferlin deficiency causes proximal and distal forms of muscular dystrophy, which are known by the term dysferlinopathy.
Furthermore, genetic disruption of the central component (C3) of the complement system ameliorated muscle pathology in dysferlin-deficient mice but had no significant beneficial effect in a genetically distinct model of muscular dystrophy, mdx mice.
Dysferlin mutations cause inherited muscular dystrophy, and dysferlin also shows abnormal plasma membrane expression in other forms of muscular dystrophy.
Furthermore, genetic disruption of the central component (C3) of the complement system ameliorated muscle pathology in dysferlin-deficient mice but had no significant beneficial effect in a genetically distinct model of muscular dystrophy, mdx mice.