New Rare Type Of Neuromuscular Disease Identified
By C. Rajan, contributing writer
A rare new hereditary neuromuscular disorder has just been identified by an international team of researchers. The inherited condition is caused by a genetic mutation which affects the messages sent by nerves to control muscles, resulting in loss of muscle control and subsequent muscle weakening.
“This discovery gives us new insight into the mechanisms of diseases that are caused by a breakdown in neuromuscular signal transmission,” said David Herrmann, M.B.B.Ch., co-lead author of the study and a professor in the Department of Neurology at the University of Rochester School of Medicine and Dentistry. “It is our hope that these findings will help identify new targets for therapies that can eventually be used to treat these diseases.”
Neuromuscular disorders generally affect the nerves that control the body's voluntary muscles such as those in our arms and legs. When the nerve cells are unhealthy or die, there is impaired communication with the muscles, and the muscles weaken and waste away gradually. Many neuromuscular diseases are genetic and do not have a cure yet.
The focus of this research was the neuromuscular junction where the axon fibers that extend from peripheral nerves meet the muscle cells. The chemical signals that pass across the junction are essential for motor function, and communication problems at this junction are responsible for many disorders.
The researchers diagnosed this new disease in two sets of families in the U.S. and U.K. The families in the study had unique motor abnormalities different from other neuromuscular conditions, and the disease was passed from one generation to the next, affecting multiple generations. To understand the disease, the researchers compiled a genetic profile of the family members, where they studied the section of DNA code responsible for creating proteins using a whole exome sequencing technique.
They discovered that the two different families had mutations in the code that creates the protein synaptotagmin 2 (SYT2). SYT2 is present at the pre-synaptic terminal at the neuromuscular junction and helps the cells to detect changes in calcium levels. Calcium is involved in controlling the electrical function of cells and the release of acetylcholine, a chemical responsible for communication between the nerve and muscle cells.
The genetic mutation in the two families affected the ability of the nerve cells to sense the changes in calcium levels that would normally trigger the release of acetylcholine, which in turn resulted in impaired communication between the nerve and muscle cells, leading to the neuromuscular disorder.
The researchers have proceeded to use the mutation in SYT2 to create a fruit fly (drosophila) model of the disease, which will help them to better understand the neurological development of the disease. The researchers believe this will help them to develop potential new therapies to treat the condition.
The study was published last week in the American Journal of Human Genetics.