What are the genetic changes related to myofibrillar myopathy ?
Mutations in several genes can cause myofibrillar myopathy. These genes provide instructions for making proteins that play important roles in muscle fibers. Within muscle fibers, these proteins are involved in the assembly of structures called sarcomeres. Sarcomeres are necessary for muscles to tense (contract). The proteins associated with myofibrillar myopathy are normally active on rod-like structures within the sarcomere called Z-discs. Z-discs link neighboring sarcomeres together to form myofibrils, the basic unit of muscle fibers. The linking of sarcomeres and formation of myofibrils provide strength for muscle fibers during repeated muscle contraction and relaxation.  Gene mutations that cause myofibrillar myopathy disrupt the function of skeletal and cardiac muscle. Various muscle proteins form clumps (aggregates) in the muscle fibers of affected individuals. The aggregates prevent these proteins from functioning normally, which reduces linking between neighboring sarcomeres. As a result, muscle fiber strength is diminished.  At least six genes have been associated with myofibrillar myopathy. Mutations in these six genes account for approximately half of all cases of this condition. Mutations in the DES, MYOT, and LDB3 genes are responsible for the majority of cases of myofibrillar myopathy when the genetic cause is known.