HOUSTON, May 19, 2014 /PRNewswire-USNewswire/ -- A rare and mysterious neurological disorder inspired the Wilsey family of San Francisco to fund researchers at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital and the Department of Molecular & Human Genetics at Baylor College of Medicine to study and develop treatments for NGLY1 deficiency. The Wilseys' daughter, Grace, is one of only 14 known children worldwide affected by the rare condition, which is characterized by a mutation in the gene coding for N-glycanase 1, an enzyme that is thought to help recycle defective products from a cellular assembly line. Children who lack this enzyme experience varying degrees of movement disorders, suffer from developmental delays, have liver and gastrointestinal problems and cry without producing tears.
After a lengthy saga of visiting with physicians across the nation searching for answers about Grace's condition, the Wilsey family finally found the answer after a meeting with Dr. Huda Zoghbi, Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. Dr. Zoghbi examined Grace and recommended a new test called whole genome sequencing, which helped identify Grace as the second child in the world diagnosed with NGLY1 deficiency. Experts at Texas Children's Hospital and Baylor College of Medicine in Houston used the new test to decode the DNA sequence of her genome allowing them to identify abnormal genes. The technology helps patients and families understand the cause of neurologic diseases, as well as the risk of recurrence.
In Grace's case, the testing provided researchers eight different genes, including NGLY1, and they began investigating the genes in order of the likelihood that they might explain her disease.
Dr. Matthew Bainbridge, postdoctoral associate in the Human Genome Sequencing Center at Baylor, ultimately solved the mystery after scouring the medical literature and identifying another child with similar unusual symptoms which were tied to an NGLY1 gene defect.
"Having the support and engagement of the Wilsey family was critical to solving this case and their ongoing efforts in patient-research advocacy will be paramount to solving more genetic diseases in the future," said Bainbridge.
The research was published in a recent issue of the journal Genetics in Medicine (http://www.nature.com/gim/journal/vaop/ncurrent/full/gim201422a.html).
"Whole genome sequencing has been a powerful tool in diagnosing some of the most challenging cases and we are increasingly finding patients with rare syndromes who have been through a battery of previous tests without a diagnosis," said Dr. Richard Gibbs, Director of the Human Genome Sequencing Center at Baylor. Conducted by the Whole Genome Laboratory at Baylor, the academic partner of Texas Children's Hospital, the test results are interpreted by bioinformatics and clinical genetics experts who transmit the findings to a referring physician.
Hamed Jafar-Nejad, M.D., in consultation with Dr. Zoghbi, is leading research efforts for NGLY1 deficiency at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. The Baylor/NRI group is using fruit flies to understand the cellular and physiological defects caused by the loss of NGLY1 and to identify potential therapeutic targets for the disease. These studies are coordinated with those of a group of researchers around the world who are using biochemical, cell biological, mouse genetics and systems biology approaches to understand the biology of NGLY1 and the pathophysiology of NGLY1 deficiency. It is hoped that this multidisciplinary approach, which has been made possible by generous funds from the Wilsey family, will significantly expedite the progress of this project and will lead to the identification of a therapy for NGLY1 deficiency.
"We are grateful to finally have a diagnosis for Grace and we are committed to funding research efforts that will lead to a more advanced understanding of this disease and potentially a treatment or cure for Grace and other children who are affected," said Matt Wilsey, Grace's father.
About Texas Children's Hospital
Texas Children's Hospital, a not-for-profit health care organization, is committed to creating a healthier future for children and women throughout the global community by leading in patient care, education and research. Consistently ranked as the best children's hospital in Texas, and among the top in the nation, Texas Children's has garnered widespread recognition for its expertise and breakthroughs in pediatric and women's health. The hospital includes the Jan and Dan Duncan Neurological Research Institute; the Feigin Center for pediatric research; Texas Children's Pavilion for Women, a comprehensive obstetrics/gynecology facility focusing on high-risk births; Texas Children's Hospital West Campus, a community hospital in suburban West Houston; and Texas Children's Hospital The Woodlands, a second community hospital planned to open in 2017. The organization also created the nation's first HMO for children, has the largest pediatric primary care network in the country and a global health program that's channeling care to children and women all over the world. Texas Children's Hospital is affiliated with Baylor College of Medicine. For more information, go to www.texaschildrens.org. Get the latest news by visiting the online newsroom and Twitter at twitter.com/texaschildrens.
About Baylor College of Medicine
Baylor College of Medicine (www.bcm.edu) in Houston is recognized as a premier academic health science center and is known for excellence in education, research and patient care. It is the only private medical school in the greater southwest and is ranked as one of the top 25 medical schools for research in U.S. News & World Report.
Texas Children's Hospital
Veronika Javor Romeis
Baylor College of Medicine
SOURCE Texas Children's Hospital