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About SickKids

August 15, 2010

Slippery DNA holds clues to fighting diseases that progress with age: SickKids study

TORONTO – Progressive diseases are among the most dreaded kind, because they worsen over time. And as the disease goes from one generation to the next, the severity increases and the age of onset decreases. Researchers are aware of some 40 neurological, neurodegenerative and neuromuscular diseases that share a common element – they contain mutations in the form of repeating DNA that grows longer through the life of a patient, making the condition worsen. 

In an international study published in the August 15 advance online edition of Nature Structural & Molecular Biology, scientists from The Hospital for Sick Children (SickKids), along with a research team in Paris, France, uncover the workings behind this dynamic mutation.

Progressive diseases include Huntington’s disease and myotonic dystrophy (a form of muscular dystrophy) and fragile X syndrome (most common cause of inherited mental impairment). The SickKids team looked specifically at myotonic dystrophy, which is a multisystem disorder that affects skeletal and smooth muscle as well as the heart, endocrine system, and central nervous system. They found that the mutation is caused by a slippage of the DNA as it replicates. They also identified the location on the DNA where this slippage starts and which tissues are affected at various ages. 

Dr. Christopher E. Pearson, principal investigator of the study, Senior Scientist at SickKids and Associate Professor in the Department of Molecular Genetics at the University of Toronto, explains the concept behind repeat mutations:

“Consider the gene as a sentence that reads, ‘THE CAT ATE THE FAT FAT RAT’. In repeat-associated diseases, the mutation would be ‘THE CAT ATE THE FAT FAT FAT FAT FAT FAT FAT RAT’. These repeated DNAs are slippery,” says Pearson.

Myotonic dystrophy type 1 affects 1 in 8,000 worldwide, and is up to 60 times more prevalent in Quebec than elsewhere in the world.

“We are moving towards being able to treat progressive diseases by arresting or reversing the repeat mutation. In other words, we hope to be able to prevent, or even better, reduce the expansion of the number of ‘FAT’ units,’ says Pearson. “Knowing when, where and how this mutation occurs, helps us determine when and where to treat as well as what to target.”

In theory, the clinical benefit of stopping or reversing these expansions would be to reduce or reverse the progression of the disease. Over the next 10 years, the SickKids team hopes to identify compounds that can modify the mutation by inhibiting it or reversing it.

As a geneticist, Pearson’s lab will be relocated to the Genetics & Genomics in Child Health neighbourhood in the new SickKids Research & Learning Tower. This will encourage interactions with colleagues from other scientific disciplines to improve our understanding of diseases such as Huntington’s disease, myotonic dystrophy, fragile X syndrome and spinal cerebellar ataxias.

This study was supported by the Canadian Institutes of Health Research, the Muscular Dystrophy Association USA, the University of Rochester Medical Centre’s Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, France-Canada Exchange, Institut national de santé et de la recherche médicale, Association Française contre les Myopathies, Université Paris Descartes and SickKids Foundation.

To watch Dr. Christopher E. Pearson discussing this breakthrough on our YouTube channel, visit www.youtube.com/sickkidsinteractive.

About The Hospital for Sick Children
The Hospital for Sick Children (SickKids) is recognized as one of the world’s foremost paediatric health-care institutions and is Canada’s leading centre dedicated to advancing children’s health through the integration of patient care, research and education. Founded in 1875 and affiliated with the University of Toronto, SickKids is one of Canada’s most research-intensive hospitals and has generated discoveries that have helped children globally.  Its mission is to provide the best in complex and specialized family-centred care; pioneer scientific and clinical advancements; share expertise; foster an academic environment that nurtures health-care professionals; and champion an accessible, comprehensive and sustainable child health system.  SickKids is proud of its vision of Healthier Children. A Better World.™ For more information, please visit www.sickkids.ca. 

About Peter Gilgan Centre for Research and Learning 
The Peter Gilgan Centre for Research and Learning will bring together researchers from different scientific disciplines and a variety of clinical perspectives, to accelerate discoveries, new knowledge and their application to child health — a different concept from traditional research building designs. The facility will physically connect SickKids science, discovery and learning activities to its clinical operations. Designed by award-winning architects Diamond Schmitt Architects Inc. and HDR Inc. with a goal to achieve LEED® Gold Certification for sustainable design, the Gilgan Centre will create an architectural landmark as the eastern gateway to Toronto’s Discovery District. The Peter Gilgan Centre for Research and Learning is funded by a grant from the Canada Foundation for Innovation, the Government of Ontario, philanthropist Peter Gilgan and community support for the ongoing fundraising campaign. For more information, please visit www.sickkidsfoundation.com/bepartofit.


For more information, please contact:

Matet Nebres
The Hospital for Sick Children
Phone: 416-813-6380
email: matet.nebres@sickkids.ca

Suzanne Gold
The Hospital for Sick Children
Phone: 416-813-7654 ext. 2059
email: suzanne.gold@sickkids.ca