Gene discovery: When you’re the only patient with the disease

Gene Discovery Core rare diseaseVector took a moment this morning at the Boston Children’s Hospital Global Pediatric Innovation Summit + Awards to catch up with the Gene Discovery Core at the Manton Center for Orphan Disease Research. Its exhibition table doesn’t have fancy mannequins or flashy screens, but this team is rocking genetics and genomics, one patient at a time.

The usual methods for finding disease-causing genes don’t work for many patients who walk in the doors of Boston Children’s, or who mail in samples from all over the world. They may be one of just a handful of patients in the world with their condition—which may not even have a name yet.

“The conundrum for ultrarare conditions, where you have an ‘n’ of 1, is that even if you find a candidate gene, you still have to prove its role functionally—creating mouse models and zebrafish models to see what the gene does,” says Meghan Towne, a genetic counselor with the Gene Discovery Core.

That’s a lot of hands-on work. It requires labs and clinical experts in all the different organ systems the disease may affect. “As many brains as you can get thinking about this patient, the better,” says Towne.

Here are their results so far:

  • 651 families enrolled
  • 256 had no known candidate gene for their condition, so underwent DNA sequencing (usually exome sequencing)
  • 167 families had data returned (the others are still in progress)
  • 38 families had a gene discovered from this process, and 69 had candidate genes flagged that need further study to pin down the connection.

The Core is going to be the foundation of the Undiagnosed Disease Network at Boston Children’s—in fact, it’s one of the reasons the National Institutes of Health chose the hospital as one of the sites.

Keep following Taking on Tomorrow at our live site. At 2:10 today Eastern, the Manton Center will take part in a panel entitled “Rare Diseases: Lessons from the Path Less Chosen.Our hashtag is #PedInno14.