| Dysferlinopathy |
| Dae-Seong Kim |
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| ABSTRACT |
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Dysferlinopthy refers to a group of autosomal recessive muscular dystrophy caused by mutations of dysferlin gene (DYSF). The DYSF is located on chromosome 2p13, contains 55 coding exons and spans 150 kb of genomic DNA. The transcript is 6.3 kb large and is mainly expressed in skeletal muscle at the sarcolemmal membrane. Dysferlin is a key calcium ion sensor involved in the Ca2+-triggered synaptic vesicle-plasma membrane fusion process, and plays a role in the sarcolemmal membrane repair mechanism of skeletal muscle fibers that permits rapid resealing of membrane disrupted by mechanical stress. Three main clinical subtypes of dysferlinopathy consist of Miyoshi myopathy (MM), limb-girdle muscular dystrophy type 2B (LGMD2B), and distal myopathy with onset in tibialsis anterior (DMAT). Regardless of their clinical phenotype, patients with dysferlinopathy share common features such as onset in late teens to early twenties, slow progression, extremely high serum CK levels, and loss of dysferlin on immunohistochemistry (IHC) and Western blot (WB). Muscle imaging is helpful for the evaluation of the degree of affection in different muscle groups and monitoring the progression of the disease. On muscle biopsy, it is frequently associated with inflammatory cellular infiltrates, and should be differentiated from polymyositis in order to avoid unnecessary treatment. IHC or WB is the golden standard for the diagnosis of dysferlinopathy. Although DNA test for the identification of DYSF mutations can further help to confirm the disease, high risk of diagnostic errors related to the large gene size can limit its usefulness as a reliable diagnostic test. |
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