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Sarcolemmal proteins and the spectrum of limb-girdle muscular dystrophies.

Proteins of the sarcolemma are of crucial importance for the pathogenesis of muscular dystrophies. This update focuses on the dystrophin-associated proteins including the dystroglycan and sarcoglycan complexes, caveolin-3, dysferlin, and the extracellular matrix component collagen type VI. The molecular findings are correlated with some of the clinical phenotypes that are part of the limb-girdle muscular dystrophy spectrum, including fukutin-related proteinopathy (LGMD 21), the sarcoglycanopathies (LGMD 2C-F), caveolinopathy (LGMD 1C), dysferlinopathy (LGMD 2B), and finally Bethlem myopathy. Although recent progress has been tremendous, much remains to be learned about the pathophysiological consequences caused by a deficiency of any one of these components.