Genome study solves US twins' mystery illness

When Noah and Alexis Beery were diagnosed with cerebral palsy nearly 13 years ago, the diagnosis never sat right with the twins' mother, Retta Beery.

Her lengthy search for the true cause of her children's strange collection of symptoms finally led to an answer when a scan of the twins' genomes turned up a genetic defect that caused the children's disorder and finally led to the right treatment.

The investigation offers a rare glimpse at the potential of whole genome sequencing - now largely reserved for research - at improving the treatment of individual disease.

The study

Now, the once-disabling disorder that caused involuntary spasms and left one twin unable to walk is all but gone, and both teens are thriving in school and playing sports.

"If you saw them today, you'd say there was nothing wrong with them," said Dr Matthew Bainbridge of Baylor Genome Sequencing Centre in Texas, whose research appeared in Science Translational Medicine.

At a cost of $10,000 to $20,000 per patient, whole genome sequencing is still out of reach for most people, but companies such as Illumina, Life Technologies Corp and Roche Holding are working to bring the cost down.

The findings

Beery's relentless search previously led the children to Dr John Fink of the University of Michigan, who diagnosed them, then at age 5, with dopa-responsive dystonia (DRD), a complex movement disorder involving the loss of dopamine.

The muscles of people with dystonia contract and spasm involuntarily. When the twins were given L-dopa, they responded quickly.

But there were still some lingering symptoms, and six years ago, Alexis developed a cough that became increasingly debilitating.

"About a year and a half ago it turned from this horrible cough into this massive breathing problem. We were back in the arena of specialists, trying to figure out what was going on," Beery said.

As luck would have it, the twins' father had recently taken a job as chief information officer for Life Technologies, maker of gene sequencing machines.

With his wife's prodding, the couple approached the company and asked if their children could have their genomes sequenced through a joint project with Baylor.

"They approached us and asked if we would be willing to do it. We didn't know how it would turn out," Bainbridge said.

When the researchers analysed raw DNA sequence data from the twins' genomes, they were surprised to find no mutations in the two genes commonly mutated in DRD.

A mutated gene

Instead, the team discovered that the twins carried a mutated gene related to serotonin production that made them deficient in both dopamine and serotonin.

Adding serotonin-inducing 5-Hydroxytryptophan (5-HTP) to their dopamine regimen improved their symptoms dramatically after just a few weeks.

"Now, because of the sequencing, Alexis started on this new amino acid and she started back in track in March," Retta Beery said. "She's been winning races."

While the cost of sequencing puts this technology out of reach for most families, Bainbridge thinks it will soon be affordable as sequencing costs continue to fall.

He said currently the price of sequencing is dropping by half every six months.

"It's our hope that in two years or maybe even a year whole genome sequencing will be more widely available," he said.

"We'd like everyone to be able to have this." (Reuters Health)

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