The SGCE gene provides instructions for making a protein called epsilon (ε)-sarcoglycan, whose function is unknown. The ε-sarcoglycan protein is found within the cell membranes of the lungs, liver, kidneys, and spleen, but it is most abundant in nerve cells (neurons) in the brain and in muscle cells. Researchers suspect that in the brain the ε-sarcoglycan protein plays a role in the functioning of synapses, which are the connections between neurons where cell-to-cell communication occurs.
People inherit one copy of most genes from their mother and one copy from their father. Both copies are typically active, or "turned on," in cells. The SGCE gene, however, is active only when it is inherited from a person's father. This sort of parent-specific difference in gene activation is caused by a phenomenon called genomic imprinting.
More than 65 mutations in the SGCE gene have been found to cause myoclonus-dystonia. Most of these mutations lead to an abnormally short, nonfunctional ε-sarcoglycan protein that is quickly broken down. Other mutations prevent the protein from reaching the cell membrane where it is needed. The protein shortage seems to affect the regions of the brain involved in coordinating movements (the cerebellum) and controlling movements (the basal ganglia). Thus, the movement problems experienced by people with myoclonus-dystonia are caused by dysfunction in the brain, not the muscles. A shortage of functional ε-sarcoglycan protein in the brain leads to the involuntary movements characteristic of myoclonus-dystonia.
Myoclonus-dystonia occurs when mutations affect the paternal copy of the SGCE gene. More than 95 percent of individuals who inherit an SGCE gene mutation from their mothers do not show symptoms of the disease. Rarely, individuals who inherit a SGCE gene mutation from their mothers will develop features of myoclonus-dystonia. It is unclear why a gene that is supposed to be turned off is active in these rare cases.
- sarcoglycan, epsilon