Gene Summary
RefSeq / NCBIThe protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]
Clinical Phenotype
Dysferlinopathy: includes LGMD2B/R2 (proximal pelvic-girdle weakness) and Miyoshi myopathy (distal weakness, gastrocnemius > tibialis anterior). CK is dramatically elevated (10,000–100,000 IU/L). Onset typically in late teens to 20s.
Molecular Mechanism
Dysferlin is a calcium-activated membrane repair protein; when muscle membrane is torn (e.g., during eccentric exercise), dysferlin mediates membrane resealing. Loss leads to impaired repair, chronic microinjury, and degeneration — despite initially excellent athletic performance in many patients.
Clinical Hallmarks & Key Evidence
Many LGMD2B patients were champion athletes before symptom onset — the muscle membrane tears of intense exercise had been compensated by dysferlin-mediated repair.
Klinge L et al. Neuromuscul Disord. 2010;20(6):380-85.
Markedly elevated CK (often >10,000 IU/L, sometimes >100,000 IU/L) at a young athletic patient warrants dysferlinopathy workup even before weakness develops.
Illa I et al. Ann Neurol. 2001;49(6):811-15.
Dysferlin protein can be detected by monocyte flow cytometry — monocytes express dysferlin and the test is a reliable, minimally invasive screening tool.
Ho M et al. Ann Neurol. 2002;51(5):669-72.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.