News 2013

Toronto, Ontario, Thu Jul 25 2013
By: Jane Gerster Staff Reporter, Toronto Star

Sick Kids genome project opens door to more treatment options

The world's largest genome clinic devoted to unearthing new and custom treatment options for common and fatal pediatric diseases officially opens at the Hospital for Sick Children this month, launching a new era of genetic medicine.

The clinic, part of a five–year research project supported by the hospital's Centre for Genetic Medicine, will offer whole genome sequencing to roughly 100 children each year, with priority going to patients with eye diseases, kidney disorders, heart problems and metabolic and inflammatory diseases.

Until now, whole–genome sequencing, which maps a person's entire DNA, or genetic blueprint, has been considered an expensive process reserved for narrowly focused research areas, including autism studies. It is rarely drawn on as a tool for designing everyday treatment plans. More often, doctors use limited, cheaper sequencing techniques like exome sequencing, which is a process that looks at just 1 per cent of the genes (those producing proteins) to make appropriate treatment decisions.

"The patients we have here are being managed as well as we know and as well as everybody knows around the world," said Dr. Ronald Cohn, co–director of the Centre for Genetic Medicine. "But … very often you find things in your genes which open up a different kind of management."

Adding the whole spectrum of genes could provide enough information to allow doctors to individualize medicine and more effectively treat common diseases like cancer. Whole–genome sequencing may find new genes both for treatable and incurable disorders, such as retinitis pigmentosa, a degenerative eye condition that eventually leads to blindness, which can open up new treatment possibilities.

Although the clinic has seen only a handful of children so far and no findings have been definitively proven, preliminary results show how sequencing can change a person's clinical diagnosis.

James Villalobos–White is one of the genome clinic's first patients. Since he was 2, his mother, Nicola White, has ferried him to and from specialist appointments looking for answers. "They thought he needed glasses, but said his muscles looked OK," she said. "Then we were going every six months and the glasses didn't work."

His journey to diagnosis ended last March.

It's not uncommon for kids to be shuttled from department to department looking for answers, said Dr. Stephen Meyn, the program head for genetics and genome biology at Sick Kids.

"If the extra information can show maybe the clinical diagnosis was incorrect . . . it may change his diagnosis and prognosis," Meyn said.

Now that James' family finally has a reason why their 6–year–old boy seems a little clumsier at times than most kids and reads books very closely and from an odd angle, they want to know everything they can.

"If you have the information, you can be proactive," White said, adding it never occurred to her to say no when James was offered a spot in the genome clinic. James has ocular albinism, a condition that, by reducing the amount of colour in the iris, affects vision.

"We have a lot of health issues in our family," she said. "It's good to know and stay on top of it."

The family is expecting James' preliminary sequencing information by the end of the summer.

His diagnosis doesn't change his day–to–day life too much, and James is consumed by frog–catching and kayaking. He only pays attention to his disease when doctors take his blood, which he hates.

The information the family gets back, though, could change his future.

It will tell them whether James' albinism extends past his eyes (he is much, much fairer than his parents), whether he has any other genetic disorders, and it could tell them what his likelihood is of inheriting the cancer gene that runs in his family.

Making the decision is very profound, said Cohn, who had his whole genome sequenced to personally understand the experience.

Although he didn't find anything "too bad," he did discover an elevated risk for thyroid cancer and a mutation negatively affecting his metabolism, meaning he needs to work a little harder than the average person if he wants to lose weight.

"Think about what it means when you offer somebody this and what it does to them," he said. "Some of my colleagues said, 'Oh, I think I would like to do it' … and some of them said, 'I don't know, I have to think about it.' It's a really powerful experience to think about."

Cost aside, sequencing all the 20,000 to 25,000 genes in the human genome not only has the potential to answer questions about a disease an individual is known to have, but also whether there are any other genetic disorders present and the person's likelihood of developing adult–onset disorders.

Figuring out what role the sequencing can play in treatment and what ethical considerations are needed to make it an effective diagnostic tool for doctors everywhere is where Sick Kids' genome clinic - broad in scope - will play a crucial role.

The process isn't as easy as simply adding whole–genome sequencing to the list of tests doctors can run, since the test can reveal a whole host of unsolicited findings which don't directly relate to the initial disorder - which is controversial.

Tim Caulfield, a Canada research chair in health law and policy, said the unsolicited findings are the subject of "raging debate" in the legal and bioethical community.

"There are many challenges," Caulfield said, beyond just what to do with the findings. "Once the information is out, (you) can't put it back," he said, which effectively removes a child's genetic autonomy, not to mention fans the flames of concern over possible genetic discrimination.

White and her husband, Diego Villalobos, made the choice for their son.

"I'm his mother," White explained, "and I think I need to make decisions for him."

Not everyone agrees, and debate over a child's genetic autonomy is heightened around disorders such as Huntington's disease, a fatal disease causing several neurological and psychiatric symptoms that usually presents itself when a person is in their 30s or 40s.

Some people argue that a child still has time to make his or her own decision once they turn 18, and parents shouldn't make it for the child, since the information could negatively affect someone growing up.

The Sick Kids project will avoid that particular ethical issue by specifically excluding analysis of genes that affect late–onset conditions for which there is "no possibility of medical intervention," Dr. Meyn said.

Despite the ethical considerations, Caulfield said he is fascinated by the project, just a little skeptical: "You're producing a massive amount of variant information of unknown clinical and health value."

The Sick Kids' genetics team believes wading through that data and navigating the murky ethical waters will be worth the risk, paying off for sick children around the world who sometimes go years without an official diagnosis, or spend the majority of their all too short lives in the hospital, battling incurable diseases.