Our genes are the instruction manuals to proteins. Proteins play a key role in all the tasks that keep our bodies working properly. For example, the collagen VI protein is part of the protective and supportive environment that surrounds muscle cells – called the extracellular matrix. Changes can happen to the instructions, which means proteins are made differently. These altered proteins can cause damage to the cells. When the collagen VI protein is changed, it can cause the environment outside of muscle cells to provide less support and protection. This can lead to muscle damage and cause congenital muscular dystrophies, such as Bethlem myopathy and Ullrich congenital muscular dystrophy (UCMD).
There are several genes involved in making the collagen VI protein. The process involves making a copy of the collagen VI genes (known as RNA), which are transported to the protein making machinery in the cell. Professor Bonnemann and team have identified a change to the COL6A1 gene (called the COL6A1 c.930+189C>T variant). This leads to the addition of an extra piece of genetic sequence to the copy of the COL6A1 gene (called a pseudoexon). The researchers have shown that the addition of this genetic sequence means the collagen VI protein causes damage to environment outside of the muscle cells, leading to a severe form of collagen VI-related muscular dystrophy.