LDB3

The LDB3 gene provides instructions for making a protein called LIM domain binding 3 (LDB3). The LDB3 protein is found in heart (cardiac) muscle and muscles used for movement (skeletal muscle). Within muscle fibers, LDB3 proteins are found in structures called sarcomeres, which are necessary for muscles to tense (contract). This protein attaches (binds) to other proteins and is involved in maintaining the stability of rod-like structures within sarcomeres 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 cycles of muscle contraction and relaxation.

Several different versions (isoforms) of the LDB3 protein are produced from the LDB3 gene.

myofibrillar myopathy - caused by mutations in the LDB3 gene

At least three mutations in the LDB3 gene have been found to cause myofibrillar myopathy. These mutations change single protein building blocks (amino acids) in the LDB3 protein. Mutated LDB3 proteins cluster together with other muscle proteins in the sarcomere to form clumps (aggregates). The aggregates prevent these proteins from functioning normally. A dysfunctional desmin protein cannot properly interact with Z-discs, leading to abnormalities of sarcomere structure and problems with the formation of myofibrils. LDB3 gene mutations that cause myofibrillar myopathy impair the function of muscle fibers, causing weakness and the other features of this condition.

other disorders - caused by mutations in the LDB3 gene

Mutations in the LDB3 gene also cause a form of heart disease called dilated cardiomyopathy. This condition enlarges (dilates) and weakens the cardiac muscle, preventing it from pumping blood efficiently. Although cardiomyopathy is a sign of myofibrillar myopathy, some cases of dilated cardiomyopathy caused by LDB3 gene mutations are not associated with weakness of the skeletal muscles. Researchers have identified at least two mutations in the LDB3 gene that cause dilated cardiomyopathy without the other features of myofibrillar myopathy. These mutations, written as Asp117Asn and Lys136Met, change single amino acids in the LDB3 protein. Researchers are not certain why some mutations in the LDB3 gene cause dilated cardiomyopathy instead of myofibrillar myopathy.