Study Finds an Abnormality in RNA May Lead to Congenital Myotonic Dystrophy

Muscular dystrophy (MD) is a group of genetic disorders that cause the muscles of the body to weaken and fail over time. There are multiple forms of MD, all characterized by gene mutations. Each type affects patients differently and in different areas of the body, as well as at different ages, but they are usually diagnosed during childhood. 

This is a disease that typically runs in families. Although not all relations may become afflicted, usually, everyone in the family is a carrier of the gene. When they produce a child with someone else who also has the gene, the ensuing child has a 50% chance of developing MD. In extremely rare cases, MD can develop spontaneously even if neither parent is a carrier of the gene, but the offspring experiences a spontaneous mutation in their own genes.

Muscular dystrophy alters the genes that contain the information needed by cells to make a protein that controls muscle functions such that they’re either unable to create the protein or do not make enough of it, or they make mutated, unusable forms of the protein. For instance, those with Becker and Duchenne muscular dystrophy don’t produce enough of the protein dystrophin, which makes the muscles strong and protects them from injury.

It is a progressive disease that has no cure, and the outcome for most patients is generally the same: the majority of those diagnosed with MD will end up in a wheelchair. However, this isn’t a death sentence; with the right therapies, support, and some adaptations to cater to the needs of the disease, many are able to live longer, active lives. Under the umbrella term “MD,” there are nine forms of the disease that manifest differently, affect different parts of the body, and develop at different times.

Because muscular dystrophy affects the muscle, the joints may weaken in order to keep the bones strong and functioning as much as possible. Doctors believe an error in some part of the dystrophin protein affects the brain’s neuron connection and thus disrupts message transmission. This then causes various neurological deficiencies. In patients with Duchenne muscular dystrophy, an error occurs in the exon chains on the dystrophin gene, making the instructions to create the dystrophin protein incorrect. Many cases have different mutations of exon chains, but the only way to find them is through genetic testing. Becker dystrophy has a slower rate of decline and is a milder form of the disease. Researchers thought it possible to create partially functioning dystrophin protein using the process that happens organically in Becker dystrophy, and in some forms of MD, this protein could be applicable.

Scientists have studied the ways sarcomeres and telomeres impact MD. Every cell in the body contains telomeres, which help with chromosome organization and the replication of cells. As people get older, the cells start creating copies to replenish themselves, and the more they do this, the shorter the telomeres become until they can no longer function well, causing cell aging. 

A sarcomere is a unit of striated muscle in the human body. Some of these are made of muscle fibers comprised of thick and thin microfibril strands. The thick filament is made by myosin and thin filament is made by actin. These are organized into repeating subunits known as sarcomeres. The capacity of a sarcomere to contract is vital for one’s muscular health. 

Myotonic dystrophy is a common form of MD. It is inherited and can affect both men and women equally. The symptoms may appear at any time throughout a person’s life. It causes weakness in the extremities, but it can also affect other muscles. This disease progresses slowly and eventually results in weakness and loss of function in other muscle groups. A very serious form called Thomsen’s disease may appear in newborns. The mothers of these affected infants usually have myotonic dystrophy (DM) themselves.

DM1 is the most common form of DM and is caused by a mutation of the dystrophin protein kinase gene, which is located on the 19q chromosome. This gene is a trinucleotide repeat expansion that develops a dynamic mutation during DNA replication, caused by slippage. Over the course of the patient’s life, these mutations degenerate nerve cells.

Compared to genetic testing, the diagnostic process of this disease is not difficult. There are no real treatment protocols in place for it, and so therapy is tailored according to the specific needs and symptoms of each patient. Prenatal testing can be done for pregnant women who have some form of MD.

Researchers are looking to create new gene therapies through the discovery of RNA processing failure to either halt or entirely prevent some forms of congenital disease. Many women with MD hope that, through this research, they can become pregnant without passing the congenital defect on to their children.