What Really Matters

Next Generation Sequencing: Discovering Genetic Causes of Rare Diseases

DNA sequencing has helped researchers at the Children’s Hospital of Eastern Ontario (CHEO) to discover the genetic cause of 85 new rare diseases, giving patients a definitive diagnosis and opening doors for the development of effective treatments.

When she was ten years old, India began experiencing seizures. As the severity and frequency of her symptoms increased, anti-epileptic medications began to lose effect. After a five-year odyssey of ongoing testing, consultations, and biopsies, the only thing India’s family knew for certain was that she didn’t have any of the usual genetic markers of epilepsy. Without a clear diagnosis, doctors were unable to identify an effective treatment for India’s rare condition.

In 2013, India enrolled in a novel next generation sequencing study led by Drs Kym Boycott, Alex MacKenzie and David Dyment as part of a project called CARE for RARE at the Children’s Hospital of Eastern Ontario (CHEO). CHEO’s state-of-the-art DNA sequencing pipeline allowed Dr. Dyment to identify the genetic cause of India’s symptoms—the ASAH1 gene—providing India and her family with a diagnosis of spinal muscular atrophy and progressive myoclonic epilepsy (SMA-PME), an extremely rare epilepsy syndrome.

Dr. David Dyment, Clinical Investigator, CHEO Research Institute
Dr. David Dyment, Clinical Investigator, CHEO Research Institute

Next Generation Sequencing Improving Rare Disease Diagnosis

Since completion of the Human Genome Project in 2003, there has been a demand for cheaper and faster DNA sequencing methods. Where previous sequencing platforms looked at one gene at a time, next generation sequencing (NGS) platforms can sequence millions of DNA fragments in unison.

Currently, 25% of rare disease patients wait 5-30 years for a diagnosis; 40% initially receive a misdiagnosis; and half will never receive a diagnosis. In contrast, the NGS method used in the CARE for RARE lab at CHEO results in an accurate and rapid diagnosis for many patients affected by rare diseases. Securing a clear diagnosis means that patients and families can make future projections about their healthcare, tap into best practice guidelines, seek reproductive counseling, and potentially start therapies. For researchers and clinicians, it means developing effective treatments for the patients who need them. So far, the CARE for RARE team has provided a diagnosis to over 1000 patients, and has identified over 85 new rare disease genes.

India’s Contribution: Advancing Research for Children with Rare Epilepsy Disorders

Diagnosis is the critical step in ultimately determining appropriate treatment and discovering a cure—but it is just the first step; this is something patients with rare disease know too well. Tragically, in 2013, India passed away due to complications of her disease. India’s family, though devastated by this loss, takes hope that India’s diagnosis will open doors for further study on SMA-PME and other rare seizure syndromes that might save the lives of other children. Dr. David Dyment and his research colleagues at CHEO and the University of Ottawa are actively studying the ASAH1 gene to understand the mechanism of the disease, develop a therapy, and prevent future loss of life.

“We have identified a second patient in Ottawa with this rare syndrome, and there may be many other children in Canada with this condition that are, as yet, undiagnosed,” said Dr. Dyment. “It’s because of India that we know what we’re looking for, and we can move research forward to treat—and hopefully one day cure—this rare condition.”

A Diagnosis, Treatment, Cure: The Mission of the CARE for RARE Lab

CARE for RARE is a nation-wide research program focusing on the improvement of both the diagnosis and treatment of rare diseases. The lab is advancing rare disease research globally, under the leadership of Dr. Kym Boycott on the diagnostic side, and Dr. Alex MacKenzie on the treatment development side. Although led out of CHEO, CARE for RARE includes 21 academic sites across the country, and is recognized internationally as a pioneer in the field of genomics and personalized medicine.

Only 5% of children with rare disease today have access to an effective treatment. By investigating approved drugs for effectiveness in other diseases, CARE for RARE hopes to identify novel therapies for those rare diseases currently without any treatment. Together, 80 physicians and 50 scientists work to advance rare disease research as part of the CARE for RARE program. Only discovered in 2012, SMA-PME research is still in early stages.

In a statement from the Canada Foundation for Innovation, Dr. Boycott highlighted the mandate of CARE for RARE: “Whether it is two children or 200 suffering from a rare genetic disease in Canada, our goal remains the same: use state-of-the-art infrastructure, funded in part by the CFI, to rapidly diagnose their disease and then develop sustainable therapies that will make a tangible difference in the lives of our young patients and their families.”

Researchers—and the inspiring patients and families—involved with CARE for RARE are contributing to a healthier Ontario. We want to extend our sincere thanks to India’s family, who, despite their grief, have allowed us to tell India’s story and share the message that health research is essential for patients. To learn more about CARE for RARE, visit: http://care4rare.ca/


This research is one example of how CHEO and the CARE for RARE team are contributing to a healthier, wealthier, smarter Ontario. Learn more at www.healthierwealthiersmarter.ca