Superfast DNA sequencing is saving children’s lives. The technique has helped doctors in London quickly diagnose rare disorders in 10 critically ill children, enabling clinicians to give better treatment and protect some from life-threatening complications.
It took over a decade and around $2.7 billion to fully sequence the first human genome, but recent advances in technology have sped up the process and led to a fall in price. A team at London’s Great Ormond Street Hospital for Children has now used rapid whole-genome sequencing to diagnose children with unknown illnesses in intensive care, as these children often have rare genetic conditions.
“These kids are so incredibly ill,” says at University College London, who worked with the doctors. “They may have trouble breathing, their heart may not be working well.” In such cases, it is hard to know what the cause is, he says. “But if you can find a genetic diagnosis, it really helps the clinicians.”
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Preventing harm
The team cut the time it takes to give a genetic diagnosis from weeks to as little as four days by changing the settings on DNA-sequencing machines, using faster analysis software and getting hospital staff to prioritise urgent DNA samples.
Of the 24 children whose genomes were sequenced, 10 received a diagnosis. This led to . For one child who had failing kidneys, genomic sequencing revealed that the cause was a rare mutation, which also leads to recurrent kidney tumours. As a result, doctors realised they needed to remove both kidneys, before tumours could develop.
A child with a ruptured spleen was found to have vascular Ehlers-Danlos syndrome, which weakens internal tissues. Up until diagnosis, clinicians had suspected the child’s parents had been the cause of their injury, but the DNA results avoided a police investigation. A third child had a hormone disorder, and doctors changed how they managed the condition after diagnosis.
When a child has serious and unexplained medical symptoms, it can often lead to repeated painful diagnostic procedures (see “Quest for diagnosis”, below). To keep costs down, doctors usually get only one or several genes sequenced at a time. There are thousands of genetic diseases, and as it can take weeks to get the results from each test, families can endure years of uncertainty. But Williams’s team has shown that rapid genome sequencing is possible and cost-effective. It cost £5600 to analyse each child’s genome – only a little more than the cost of a day in intensive care.
“It’s pretty clear it’s going to transform intensive care practice,” says Stephen Kingsmore of the in San Diego. “For the families this is totally miraculous.”
While four days for sequencing and analysing a genome using standard hospital equipment is impressive, Kingsmore’s team has managed even faster results using specialist sequencing equipment that isn’t yet widely available. Their fastest time to a genomics-based diagnosis is 19.5 hours.
His team has reported using this technology to get diagnoses for . In one case, they were able to diagnose a rare form of epilepsy in a newborn baby, leading to successful treatment that prevented the baby getting severe brain damage.
A diagnosis is valuable even if a child’s condition is fatal, says Williams. “If you know there’s nothing you can do then you don’t have to keep doing biopsies and you can make them more comfortable – that’s a real godsend,” he says.
Not all children who have their genome sequenced get a diagnosis, because we don’t yet know all the genetic variants responsible for various conditions. However, knowledge is growing, thanks in part to efforts such as the UK’s 100,000 Genomes Project, which is sequencing the DNA of people with rare diseases and cancer.
Quest for diagnosis
“They call it a diagnostic odyssey,” says Louise, whose 8-year-old son Scott has an unknown condition that causes epilepsy and learning disabilities.The search for a diagnosis can dominate the lives of children with unknown conditions. Scott has had his brain activity monitored many times – a process that requires him to stop taking his epilepsy medication. This leads to more seizures, and can result in a week’s stay in hospital. Biopsies can require general anaesthetic. “It’s awful for such a young child to have to go into hospital yet again, and to have the pain when they come round afterwards,” says Louise.
When Scott was 4, his family decided not to have any further invasive tests. “We needed to live some form of normality,” says Louise.
The family has now agreed to have Scott’s genome sequenced as part of the UK’s 100,000 Genomes Project. If a genetic variant that has caused his condition is identified, the family may finally have a diagnosis, which could mean he gets better treatment.
This article appears in print under the headline “Genomics saves lives”
