Genomic Copy Number Variation in Cerebral Palsy

IN BRIEF © RICHARD F. WINTLE, 2017

Introduction

Scientists have known for many years that changes in genes can result in disorders that affect the muscles as well as the nervous system. Those genes involved in building parts of the nervous system, creating muscle and making strong blood vessels can have alterations in them that result in them not working properly. Scientists have identified many genes involved in neurodevelopmental and neuromuscular disorders, such as autism and muscular dystrophy. This study’s goal was to investigate whether changes in genes could also have effects that result in cerebral palsy (CP).

Research Question

Do changes in genes occur in persons with CP and, if so, how do these changes affect their muscles and nervous system?

How did researchers answer this question? 

Medical records from children, parents and/or guardians were sourced and reviewed so we could fully understand the type of CP each one had. Then, saliva (spit) samples from all family members were obtained from which DNA was extracted. A technology called “microarrays” or “gene chips” was used to determine if any genes were changed. By changes, we mean that either genes were missing (deletions) or that there was extra genetic material (duplication). We call these changes Copy Number Variations, or CNV’s. They’ve also been referred to as Copy Number Variants. One or more genes can be affected.

What did we learn?

We found that CNV’s occur more frequently in individuals with CP than in the general population. In this study, 7%, about 1 in 14 children had a “de novo” change, meaning it was not inherited from either parent. The change did indeed affect at least one gene that we would expect to affect the development or function of their nervous system, muscles, or both. We were surprised by these findings as the percentage of “de novo” changes was much higher than anticipated, but in fact they turned out to be similar to results of studies by other researchers in Israel and Australia.

Implications

This study demonstrated that genetic testing may help doctors recognize CP earlier. Our understanding of neuroplasticity – the brain’s natural ability to change and adapt – indicates that a child’s brain is most likely to respond to treatment during the first few years of life. Therefore, earlier recognition of CP may allow for earlier intervention and better outcomes.

Future Steps

By carrying out further studies, we will be able to find out more about genes that have CNV’s, as well as about the proteins that these genes are responsible for making. With a better understanding of all the possible genes involved, we can increase our knowledge of how the nervous system and muscles develop and how they communicate with each other. Ultimately, this will make it possible to better design therapies that are specifically targeted toward the basic biology underlying cerebral palsy.

Acknowledgements

This In Brief was developed as part of the Ontario Brain Institute initiative CP-NET. We also gratefully acknowledge Kids Brain Health Network for their support of the study. 

Special thanks to JoAnne Golt Mosel, Carla Lowe, Dayle McCauley, Connie Putterman and Stephen W. Scherer for critically reviewing this document. 

For further information, please contact:

Brie Chauncey
Email: chaunceb@mcmaster.ca

References

Maryam Oskoui, Matthew J. Gazzellone, Bhooma Thiruvahindrapuram, Mehdi Zarrei, John Andersen, John Wei, Zhuozhi Wang, Richard F. Wintle, Christian R. Marshall, Ronald D. Cohn, Rosanna Weksberg, Dimitri J. Stavropoulos, Darcy Fehlings, Michael I. Shevell, and Stephen W. Scherer. Clinically relevant copy number variations detected in cerebral palsy. Nature Communications, 3 August 2015, volume 6, page 7949. This article is freely available here.