Autosomal recessive limb-girdle muscular dystrophy (AR LGMD), a genetically heterogeneous group of disorders affecting the proximal musculature, has eight distinct forms: 2A to 2H. Each of these forms is caused by specific gene mutations. A mutation in the telethonin gene causes LGMD 2G. Telethonin, a 19 kDa sarcomeric protein found in striated and cardiac muscle, has a developmentally and functionally regulated expression pattern. Telethonin transcript down-regulation occurs in response to muscle denervation. Protein levels of telethonin are partially regulated by neuronal activity, thereby linking telethonin to dynamic control of myofibrillogenesis and muscle turnover in human skeletal muscle. The telethonin transcript exhibits a pattern of accumulation typical of contractile proteins, suggesting a role for the protein in myofibrillar assembly. Immunofluorescence images show that telethonin co-localizes with myosin, which is an expression pattern typical of sarcomeric proteins. Telethonin has a known sarcomeric binding partner, titin, and is also known as titin CAP (TCAP). Therefore, telethonin plays a major role in AR LGMD 2G and is also important as a developmentally and functionally regulated sarcomeric protein.
