Powerful next generation technology may lead to better genetic testing

Complex childhood diseases – Genetic disorders

Oana Caluseriu and patient familyImagine trying to decipher a Rubik’s cube that has 20,000 components. That will give you some idea of the complexity involved in looking for the cause of rare genetic disorders. 
“It’s like trying to solve an enormously complicated puzzle,” says Dr. Oana Caluseriu, a medical geneticist who is leading a pilot study of rare genetic disorders that aims to provide personalized diagnosis and care for children and their families.
Consider the challenges. There are at least 7,000 genetic disorders and the cause of about half of these has not been established yet. Even known genetic disorders can be difficult to diagnose because the symptoms and signs can vary from person to person for the same disorder and because there may be more than one gene involved in the cause. Conventional one-gene-at-a-time testing is often impractical and prohibitively expensive. Consequently, more than half of the 280,000 Albertans, most of them children, who suffer from rare genetic disorders are not diagnosed even though they account for about a third of pediatric hospital admissions.
But there’s good news. Genetic technology has made tremendous advances in the past five years. In her study, which echoes national level studies, Dr. Caluseriu is piloting the use of a remarkable new tool called Next-Generation Sequencing (NGS) that has the potential to transform the testing and diagnosis of genetic disorders. NGS technology is able to rapidly read the 20,000 genes in the DNA that produce the proteins that code, or tell our bodies how to grow, develop and function. This coding function is sequenced and the variants — hundreds of thousands of them — are analyzed in the search for the mutated gene or genes that cause the problem. With its powerful capacity to produce and scan huge amounts of data, the new technology stands ready to pave the way for timely, cost-effective genetic testing.
“Finding a diagnosis is no small thing for families who have been struggling for years to get help for their children,” says Dr. Caluseriu. “A diagnosis offers a resolution as to why their child is different and lessens the guilt.”
By the time parents arrive at her clinic, most have already spent about seven years and on average seen eight doctors in trying to find a diagnosis for their child. The emotional and financial costs are high for both children and parents. Statistics show that a high percentage of children and caregivers suffer from anxiety, depression and isolation. Parents are often forced to seek charitable help or borrow money from their families and friends to make up for lost family income and cover additional costs.
In her pilot study with 12 families, Dr. Caluseriu aims to demonstrate the merits of combining state-of-the-art technology with individualized care management to provide children and families with accessible, quick genetic testing, genetic counselling to help parents make informed choices, appropriate support and referrals to services. It could prove to be the right combination to transform clinical care for children with rare genetic disorders — and make their lives and that of their families easier.
Dr. Caluseriu’s study is funded by an Innovation Grant supported by the Stollery Children’s Hospital Foundation.