2.1. Collagen VI-Related Myopathy

Mutations in the COL6A2 gene have been found to cause some cases of collagen VI-related myopathy, which is a group of disorders that vary in severity but generally result in muscle weakness and joint deformities called contractures. These mutations often change single protein building blocks (amino acids) in the α2(VI) chain. The most frequently affected amino acid is glycine; changes to this building block disrupt the structure of the α2(VI) chain. Other mutations can also disrupt the structure of the α2(VI) chain.

Mutations in the COL6A2 gene affect type VI collagen in different ways. Some mutations lead to altered α2(VI) chains that can be incorporated into the mature type VI collagen molecule, although they disrupt the molecule's structure and function. Other mutations result in an altered chain that cannot be incorporated at all. Still other mutations prevent the production of any functional α2(VI) chain, which impedes formation of type VI collagen. All of these COL6A2 gene mutations lead to a reduction or absence of functional collagen VI molecules. While it is difficult to predict the severity of collagen VI-related myopathy based on the type of mutation, in general, lower amounts of type VI collagen lead to more severe signs and symptoms that begin earlier in life.

Changes in α2(VI) chain structure or production lead to an unstable extracellular matrix that is no longer attached to cells through the basement membrane. As a result, the stability of muscle cells and connective tissue progressively declines, which leads to the muscle weakness, contractures, and other signs and symptoms of collagen VI-related myopathy.

2.2. Limb-Girdle Muscular Dystrophy

Limb-girdle muscular dystrophy