COL6A3

Variants (also known as mutations) in the COL6A3 gene have been found to cause some cases of collagen VI-related dystrophy, which is a group of disorders that vary in severity but generally result in muscle weakness and joint deformities called contractures. These variants often change single protein building blocks (amino acids) in the α3(VI) chain. The most frequently affected amino acid is glycine; changes to this building block disrupt the structure of the α3(VI) chain. Other variants can also disrupt the structure of the α3(VI) chain.

Variants in the COL6A3 gene affect type VI collagen in different ways. Some variants lead to altered α3(VI) chains that can be incorporated into the mature type VI collagen molecule, although they disrupt the molecule's structure and function. Other variants result in an altered chain that cannot be incorporated at all. Still other variants prevent the production of any functional α3(VI) chain, which impedes formation of type VI collagen. All of these COL6A3 gene variants lead to a reduction or absence of functional collagen VI molecules. While it is difficult to predict the severity of collagen VI-related dystrophy based on the type of variant, in general, lower amounts of type VI collagen lead to more severe signs and symptoms that begin earlier in life.

Changes in α3(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 dystrophy.

MedlinePlus Genetics provides information about Limb-girdle muscular dystrophy