Understanding the genetics of myotonic dystrophy type 1

Prof Darren Monckton

Professor Monckton and his team will investigate how the complex and changeable mutations that cause myotonic dystrophy type 1 may be linked to the extreme variability in the severity of the condition and the symptoms people experience. Understanding how a person’s genetic mutation influences the symptoms of myotonic dystrophy type 1 would help clinicians to provide more accurate information to people with the condition about how it is likely to progress and what they can expect in the future. This information will also be important for increasing the effectiveness of clinical trials.

What are the researchers aiming to do in this project?

Myotonic dystrophy type 1 is caused by a mutation called a ‘triplet repeat expansion’ in the DMPK gene. Individuals are affected when the number of repeats within the gene is increased beyond the range usually observed in the general population. The severity of the condition is at least partly due to the number of repeats; a larger number is associated with more severe symptoms and an earlier age of onset. Researchers believe that other genetic alterations, such as changes to the sequence of the DNA within the repeats, or the DNA surrounding the DMPK gene, can also dramatically influence the severity of symptoms and how the condition is inherited, although little is understood about the details of this.

In this study, Professor Monckton and his team will use cutting edge next generation DNA sequencing to determine the exact sequence and number of repeats in the DMPK gene, and also reveal genetic changes in nearby genes from people in a well-characterised Canadian population. The work will be performed in collaboration with researchers from the University of Sherbrooke (in Canada) who have substantial clinical data about the symptoms and severity of the condition in people in the population.
By comparing the genetic mutations of people from this population with clinical data about their condition and symptoms, researchers will better understand how genetic mutations in the DMPK gene and surrounding areas of DNA impact symptoms and inheritance patterns in people with myotonic dystrophy type 1.

How will the outcomes of the research benefit patients?

This research will reveal how mutations in people with myotonic dystrophy type 1 relate to the symptoms and severity of the condition which will help clinicians to provide information on the progression of the condition. This means individuals will know what to expect in the future, which can help them and their families to prepare in advance and to plan their lives around these expectations. The findings could also be useful for interpreting data from future clinical trials, where different mutations may affect the potential effectiveness of the trial treatment. This is something that would otherwise be very difficult for such a variable condition. Understanding why some individuals have unexpectedly mild symptoms may also provide new insights into potential therapies.

Grant information

Project leader: Professor Darren Monckton
Location: Glasgow University
Conditions: myotonic dystrophy type 1
Duration: three years, starting 2014
Total project cost: £177,530
Official title: Cis and trans-acting genetic modifiers of myotonic dystrophy type 1

Further information and links

Download a summary of this research project

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