The Parent-of-Origin Phenomena in Congenital Muscular Dystrophy
Muscular Dystrophy Canada is passionate about finding treatments and improving the quality of life for Canadians affected by over 150 different types of neuromuscular disorders. In order to do this, we have been dedicated to funding biomedical and discovery research to increase our understanding about these genetic disorders. Research has been successful at uncovering the causes and mechanisms behind several neuromuscular disorders, like Duchenne muscular dystrophy, there are still many unanswered questions with other conditions, like myotonic dystrophy.
Myotonic dystrophy is a rare disease. The worldwide prevalence is 14 per 100,000 people;, however, it is 30 to 60 times more common in the Saguenay-Lac-Saint-Jean region of Quebec, where the prevalence is 189 per 100,000. Myotonic dystrophy type I (DM1) has both an adult form and a congenital form. Congenital myotonic dystrophy, the most severe form of myotonic dystrophy, is almost always inherited from an affected mother; affected fathers rarely have children with the congenital form. Now, thanks to a study published in the March 2 online edition of The American Journal of Human Genetics (AJHG), there is an explanation for this “parent-of-origin” phenomena.
The study conducted by Muscular Dystrophy Canada funded researcher Christopher Pearson (Sick Kids), and Vrije Univesriteit Brussel (Belgium), found that the DNA in the mother’s eggs show a chemical change called methylation, which causes this severe form of the disorder in children inheriting the disorder from their mothers. They showed that in fathers, this methylation inhibits sperm production, which is actually a protective factor that prevents the condition from being passed down from an affected father to a child.
The Pearson research team aims to use this specific methylation in the DNA to develop a diagnostic marker for prenatal testing. Currently there is no definitive test for congenital myotonic dystrophy. Knowing that a pregnancy will result in the congenital form of the disorder will allow families to make informed decisions and prepare for the known possible outcomes.
Dr. Pearson’s lab, which has received several research grants from Muscular Dystrophy Canada’s Rachel Fund for myotonic dystrophy, is also working to find a therapeutic intervention. They are investigating drugs that would arrest or reverse the disease progression by stopping the CTG expansions that drive the progressive nature of myotonic dystrophy.