NGLY1 Hope From the Internet


Seizures, liver damage, and a limp baby were what the doctors had to work with while trying to diagnose newborn Grace Wilsey. After multiple tests, the doctors couldn’t figure out what was wrong. Eventually, the Wilsey family took the baby home. As Grace grew older, her motor development was delayed and she had hypotonia, where her muscle tone was so weakened she was often limp and floppy. The family took the baby to numerous hospitals including Johns Hopkins Hospital, the National Institutes of Health, and several children’s hospitals on the west coast. All together, the father estimates that they saw over 100 doctors. Grace was already two-years-old before they found a faulty NGLY1 gene. The extremely rare NGLY1 mutation was initially thought to be an isolated case but from research on the internet, the family finally began to find some hope.

When Grace was two, the family began whole genome sequencing at Baylor College of Medicine in Texas where they met Matthew Bainbridge, a doctorial candidate working in molecular biophysics, structural biology, and computational biology at the Human Genome Sequencing Center in Baylor. Bainbridge indicates that the first thing that geneticists search for are DNA mutations. He believes that a geneticist’s search should first be for something known before believing they are going to find something new. Once known disorders are eliminated, the hunt for unusual mutations can begin. In the case of Grace Wilsey, Bainbridge found mutations of the NGLY1 gene.

When Matthew Bainbridge began researching the NGLY1 gene, he found some online references to work that had been done in mice and fruit flies. The research indicated that the gene’s mutation could cause them to function improperly. However, this was research on laboratory animals, not humans. He continued to research and eventually found a paper published in the Journal of Medical Genetics, mentioning a young boy with a possible connection. The paper indicated that the child had a genetic disorder that could possibly be related to NGLY1 mutations. From the mention of the NGLY1 mutation came the hope that Bainbridge might be discovering a similar case, which caused Bainbridge to continue to search the internet.

NGLY1As he continued to search the internet, Bainbridge discovered a blog written by an assistant professor at the University of Utah. The man’s name is Matthew Might. Might wrote in his blog that his son Bertrand was diagnosed with a new genetic disorder and that Bertrand was “Patient 0.” Like Grace, scientists found mutations on the child’s NGLY1 gene. Bainbridge continued to read the blog posts that Might had written and found some similar symptoms. The key symptom, in Bainbridge’s mind, was the fact that like Grace, Bertrand had an inability to cry.

Bainbridge double checked with the Wilsey family as to whether or not Grace could produce tears. Kristen Wilsey, Grace’s mother, responded with an email back to the researcher. The email indicated that Grace did not really produce tears. The mother went on to further state that once or twice she had seen a large tear and sometimes Grace’s eyes would moisten but that rarely did multiple tears ever fall.

When Bertrand Might was identified with the mutations in his NGLY1 gene, the scientists at Duke University could not be certain that the mutations were the cause of Bertrand’s symptoms. With Bertrand being the only patient of which they knew, they had no one else to compare to. But after some additional research and speaking with other scientists, Bainbridge emailed Matthew Might through Might’s blog. According to Might, the email brought relief to the diagnostic odyssey with which they had been dealing. Because of the blog and because of the email, the geneticists and others caring for Grace got into contact with the scientists working on Bertrand’s case. Since that time, others have found Might’s blog. Genetic researchers and clinicians who had found mutations in the NGLY1 genes of six patients around the globe came across the blog.

They searched the internet for references to NGLY1 and from the results, found hope. The two fathers, Grace’s father Matt Wilsey and Bertrand’s father Matthew Might, teamed up to write an editorial which accompanied a paper published in a medical genetics journal. The editorial proposes new models for researchers in genetics and requests that they not underestimate the abilities of social media. At this point, the number of confirmed NGLY1 deficient patients has increased to 14, says Wilsey. A geneticist at Lucile Packard Children’s Hospital in Stanford and co-lead author of the paper, Gregory Enns, indicates that this represents a complete change in clinical medicine. He further states that it is all coming together so quickly because so many individuals are looking at the case from so many different angles.

By Dee Mueller

Journal of Medical Genetics
CNN Health

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