In California lives a little girl named Grace Wilsey who spent her infancy lethargic and staring into space. She would cry without tears, and it turns out she cannot produce them. As she aged, she exhibited motor problems and delayed cognitive development, and blood tests showed elevated levels of liver enzymes, indicating liver damage. She also experienced long bouts of hypotonia, a condition characterized by essentially lying limp like a rag doll. This was scary and frustrating for Grace’s parents, who did not know she had an as-yet unknown genetic disorder. They took her to doctor after doctor all over the country, none of whom knew what was wrong. They also did not know there were other children with this very same genetic disorder, like Grace.
In Utah, an assistant professor at the University of Utah, Matthew Might, was trying to find out what was wrong with his son, Bernard, who presented with much the same symptoms as Grace. He, too, cannot help but often be limp, and cannot do many things other children do.
After searching for answers about his son’s disorder, Might found a group of scientists at Duke University who discovered mutations on his son’s NGLY1 gene. In Texas, the Wilseys found a doctorate student at Baylor University’s Human Genome Sequencing Center, Matthew Bainbridge. After much examination of Grace’s genes to rule out other known genetic anomalies, Bainbridge found two mutations on her NGLY1 gene. He did some online research to see if there was anything already out there about this particular gene, or anyone else who had the same genetic disorder.
Bainbridge found a paper in a medical journal that described a young boy who also had NGLY1 mutations; the PhD. candidate kept digging and found Might’s blog about his son, naming the results he had been given. These indicated a possible genetic disorder. Bainbridge got excited as he noticed a growing similarity in symptoms between the children, but there was one that had not come up. He quickly got in touch with Grace’s mother, Kristen, by email. He asked her if Grace could cry, essentially, whether or not she can or cannot produce tears. When Kristen’s response was that her daughter cannot shed tears and had only produced a single full tear in her life (Grace was two or three years old by this point), Bainbridge knew the children had a disorder in common, and that they had hit on something big.
The NGLY1 gene typically produces N-glycanase 1, an enzyme that breaks down certain proteins and distributes them around the body. The mutations that Bernard and Grace exhibit (and twelve other children identified around the world since) cause structural lesions within the related gene that affect the cell’s production of this necessary enzyme. Without it, children cannot cry (caused by a congenital secretory disorder), suffer seizures, hypotonia (the rag-doll effect), have elevated liver transaminases (too much protein in the liver, hence the damage), global developmental delay (both cognitive and motor functions), a movement disorder and diminished reflexes. These are the symptoms of the genetic disorder now known as a NGLY1 deficiency.
The study on this, co-authored by Bainbridge and several others, was just published. Scientists (and parents) are excited, because they can now target research to finding specific treatments for this condition. Now that they know what the problem is, they have more of an idea what to address. Secondly, in this day and age of web connectivity, all of this came together as quickly as it did because of the Internet. People have easier and quicker access to information and each other, and the sharing of studies, both successes and failures, is becoming more common.
As in many fields, scientists can be very competitive with each other. However the mood of the day promotes greater sharing in this and many fields. Previously, information was much harder to come by, making people be private and even secretive with their work. This will undoubtedly still happen, depending on the particular study and/or personalities of those involved, but many scientists are excited by the sense of community that fosters a much more rapid pace of discovery and learning. Perhaps a cure for the NGLY1 deficiency is right around the corner.
By Julie Mahfood
Follow Julie Mahfood on Twitter @JulieWrites2