Scientists and physicians using genomics and parents tapping into the connective power of social media have identified a new genetic disease, and found the gene mutation that causes it.
The newly named disease is called NGLY1 deficiency. Described in a paper in Genetics in Medicine by the investigators who discovered it, the disease has been found in eight children with mutations in the gene encoding for N-glycanase 1, an enzyme that "recycles defective products from a cellular assembly line."
Children who do not have this enzyme have movement disorders, developmental delays, and liver problems.
They also lack the ability to shed tears when they cry. This defect is so rare that it would have taken years to find eight individuals who have it without the use of genomics and social media.
"This represents a complete change in the way we're going about clinical medicine," says Gregory Enns, an associate professor at Stanford University School of Medicine and co-lead of the new paper.
CNN relates the human side of this story, explaining how the parents of a toddler named Grace Wilsey, who suffered from some of the symptoms above and seemed impossible to diagnose, decided to get her genome sequenced at Stanford in search of an answer.
"We've probably seen over 100 doctors," Grace's father, Matt Wilsey says. "We've seen the best clinical minds in the United States."
Some of those doctors are the authors of the new paper. Grace was found to have two mutations in NGLY1, Matthew Bainbridge, of Baylor College of Medicine says. Bainbridge began hitting the literature and found a bit of work has been done on NGLY1, and he discovered one paper mentioning a young boy who had a genetic disorder that might be linked to NGLY1.
In further searches for anything related to NGLY1, Bainbridge found a blog post by Matthew Might, an assistant professor at the University of Utah.
"My son Bertrand has a new genetic disorder," Might wrote in 2012. Turns out that investigators at Duke University had used whole-exome sequencing to find that Might's son, Bertrand, had two NGLY1 mutations, which left him without glycanase 1.
"My son is the only human being known to lack this enzyme," Might wrote
But his son was not alone. When Bainbridge read Might's descriptions of Bertrand's symptoms, he saw the similarities. When he contacted the Mights and found out that Bertrand, like Grace, really could not shed tears, CNN reports, Bainbridge knew that Grace was not alone in her NYGL1 deficiency.
In a commentary in Genetics in Medicine, Matthew Might and Matt Wilsey write that this study shows the potential for the use of next-generation sequencing in diagnosing and possibly treating diseases, and how it may be particularly useful in cases of rare diseases.
They also point out how six of the eight patients in the new study were linked together after parents, physicians, or scientists who were working on isolated cases searched online for NGLY1. What they found prompted them to seek out sequencing for their children.
The two fathers have several points to make about some things that could help make sequencing more useful in the clinic – with a particular emphasis on the value of data sharing – and they also offer direct thanks for the clinical investigators who worked on their cases.