杏吧原创

Superfast DNA sequencing is聽saving children鈥檚 lives. The technique has helped doctors in聽London quickly diagnose rare聽disorders in 10聽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聽billion to fully sequence the first human genome, but recent advances in聽technology have sped up the process and led to a fall in price. A聽team at London鈥檚 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.

鈥淭hese kids are so incredibly ill,鈥� says at University College London, who worked with the doctors. 鈥淭hey may have trouble breathing, their heart may not be working well.鈥� In such cases, it is hard to know what the cause is, he says. 鈥淏ut if you can find a genetic diagnosis, it really helps the clinicians.鈥�

Preventing harm

The team cut the time it takes to聽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聽received a diagnosis. This led聽to聽. 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鈥檚 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 鈥淨uest for diagnosis鈥�, 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鈥檚 team has shown that rapid genome sequencing is possible and cost-effective. It cost 拢5600 to analyse each child鈥檚 genome 鈥� only a little more than the cost of a day in intensive care.

鈥淚t鈥檚 pretty clear it鈥檚 going to transform intensive care practice,鈥� says Stephen Kingsmore of the in聽San Diego. 鈥淔or the families this聽is totally miraculous.鈥�

While four days for sequencing and analysing a genome using standard hospital equipment is impressive, Kingsmore鈥檚 team has managed even faster results using specialist sequencing equipment that isn鈥檛 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聽child鈥檚 condition is fatal, says Williams. 鈥淚f you know there鈥檚 nothing you can do then you don鈥檛 have to keep doing biopsies and you can make them more comfortable聽鈥� that鈥檚 a real godsend,鈥� he says.

Not all children who have their聽genome sequenced get a diagnosis, because we don鈥檛 yet know all the genetic variants responsible for various conditions. However, knowledge is聽growing, thanks in part to efforts such as the UK鈥檚 100,000 Genomes Project, which is sequencing the DNA of people with rare diseases and cancer.

This article appears in print under the headline 鈥淕enomics saves lives鈥�