Inherited Diseases Found Sooner in Newborns With DNA Scan

Inherited Diseases Found Sooner in Newborns With Gene-Test Speed
Rapid whole genome sequencing was performed by researchers at Children's Mercy Hospital in Kansas City with the Illumina's HiSeq 2500. Source: Illumina via Bloomberg

Scanning the DNA of sick infants using a new speed-reading method can diagnose rare genetic disorders in two days instead of weeks, according to research that brings gene mapping a step closer to everyday hospital use.

Researchers at Children’s Mercy Hospitals and Clinics in Kansas City, Missouri, created software that takes raw data from DNA scanning machines and combs though hundreds of genetic disorders to spot disease-causing mutations. The system provided likely diagnoses for three of four sick babies in about two days, results published in Science Translational Medicine found.

The new method has the potential to make genome sequencing practical for neonatal intensive care units, enabling doctors to diagnose mysterious genetic diseases more quickly, said Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Children’s Mercy and a study senior author. Fast diagnoses of sick babies could lead to life-extending treatments sooner in some or help avoid futile, costly therapies in others.

“This is the biggest breakthrough in this technology for clinical applications we have seen in a few years,” said David Dimmock, a geneticist at the Medical College of Wisconsin and Children’s Hospital of Wisconsin in Milwaukee, who wasn’t involved in the study. “The ability to sequence and interpret a genome in less than week is huge.”

Dimmock said researchers at his institution were working on a similar fast genome interpretation system, but hadn’t published the results yet. “They beat us to the punch,” he said.

3,500 Diseases

There are about 3,500 known genetic diseases of which 500 have treatments, Kingsmore said. Many of these genetic illnesses hit young kids. Roughly 20 percent of infant deaths are caused by genetic conditions, according to the study released today.

The Children’s Mercy Hospital system was made possible in part by a new sequencing machine developed by San Diego-based Illumina Inc. that can decode an entire DNA sequence of a person in one day. This generates a colossal volume of raw data that must be analyzed by expert genetic researchers, a process that previously has taken weeks or months.

Here’s where the system devised by Children’s Mercy researchers comes into play. Kingsmore and his team devised smart software that allows treating doctors to enter in a sick baby’s symptoms. The software then matches these reported symptoms to known genetic diseases that have similar symptoms, and scans through the baby’s genome results for likely harmful mutations in relevant genes.

‘Transforming’ Neonatology

“We think this is going to transform the world of neonatology,” Kingsmore said during a conference call with reporters. “Until now, this was just not possible” to get whole genome scan results quickly enough to help sick newborns in intensive care units, he said. “Babies either died or else got better and were discharged home before the results of a gene test were returned.”

For cases in which treatments are available, spotting the cause of a disease sooner may allow treatments to be started before it is too late, he said. Kingsmore estimated the total cost of the test to be about $13,500.

The software so far includes 600 genetic diseases that affect children, Kingsmore said on a phone interview. His team plans to have all 3,500 genetic diseases entered in the system by the end of the year.

Diagnostics Movement

The research is behind a move to bring gene-sequencing technology, mostly used in academic, government and company laboratories, into hospitals and doctors’ offices for diagnostic purposes. Illumina and Carlsbad, California-based Life Technologies Corp., the two biggest makers of gene sequencing machines, have been on acquisition sprees aiming at the diagnostics market. Several Illumina researchers were co-authors on the study.

The projected two-day turnaround time for the test doesn’t include time it took to express-mail DNA samples to Illumina and for the company to send back the results on a hard drive. Including this transit time, the process took about a week, Kingsmore said. Kingsmore said he hopes to achieve the two-day time after Children’s Mercy Hospital gets its own copy of the new Illumina machine later this fall.

“They are trying to push the envelope,” said Wendy Chung, a molecular and clinical geneticist at Columbia University. “Can you not only generate the data, can you analyze and turn it around in a couple of days?”

Big Improvement

Chung said the two-day turnaround time represented “a best-case scenario” that is unlikely to be achieved in most real-world circumstances. A more realistic time for genome results would be a week, given practical considerations such as the fact that most hospital labs close over the weekend, she said. This still would be a big improvement over current methods, she said.

Chung also cautioned that there only are a minority of cases where super-fast gene scans will lead to life-saving treatments. Most severe genetic diseases don’t have good treatments, and the ones that do often can be diagnosed by other methods that don’t require every gene to be scanned.

Three of four infants that got genome scans in the study have died, according to the published results. The fourth infant is still alive, and the technology spotted a genetic defect that is the likely cause of the heart problems in this infant and his six year old brother, according to the results.

The study was sponsored by Children’s Mercy Hospital and the Marion Merrell Dow Foundation. Illumina provided free DNA sequencing for the babies in the study.

Fast Decoding

Kingsmore said he and his colleagues started testing the new software on infants after they heard about Illumina’s fast genome decoding machine early this year. They first successfully tried the software on two infants in whom the cause of disease was already known, before proceeding to use it on babies treated by the hospital with unknown diseases.

Since the study was submitted, the Children’s Mercy Hospital researchers have used the method on two additional babies, and it has found a cause in one of the two cases.

Even when there aren’t treatments for an infant, knowing what genetic disease runs in the family is helpful for parents and their relatives, Kingsmore said.

In one of the three infants who died, the scan identified the cause of a mysterious recessive disease that had previously hit several others members of an extended family, he said.

“The family was very grateful to have an answer,” Kingsmore said. “They were able to go back to their expanded family and let them know.”

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