The cause of a devastating pediatric brain disorder has been identified by a group of researchers that could pave the way for developing potential therapies for this rare neurodegenerative condition.

‘Genetic mutations in the VARS gene are known to be the culprit behind the rare neurodegenerative disorder in children.’

"These children showed epileptic seizures and abnormalities evident on brain MRI scans," said Joseph Gleeson, MD, director of neurodevelopmental genetics at RCIGM and professor of neuroscience and pediatrics at UC San Diego School of Medicine. "Although no treatment currently exists for this condition, the results are important as the first step in guiding research directed at targeted therapies." 




The genetic mutations identified in the study led to a defect in the enzyme responsible for generating proteins containing the amino acid valine which is necessary for cellular health. Genetic variations that damage these types of enzymes are associated with a variety of human diseases including microcephaly and neuropathy.
In this study, the team found that, enzymatic activity was significantly reduced in cells from the young patients. The findings suggest that children with this disorder may benefit from treatments to support the synthesis of new valine containing proteins in the brain.
For many children with genetic disabilities, the cause of their disease is rarely identified. This limits the ability of doctors to develop precise treatment plans. Researchers at RCIGM and at The McGill University and Génome Québec Innovation and Centre have pioneered the use of Whole Genome Sequencing to rapidly diagnose and guide medical management of rare childhood diseases.
Both whole exome and whole genome testing were conducted as part of this study. These tests search an individual’s genetic code for imperfections that are the source of disease.
Advertisements
Patient evaluation and testing for this study was conducted at Rady Children’s Hospital-San Diego, Montreal Children’s Hospital of the McGill University Health Centre and the National Research Center in Cairo. Medical research institutions in Amsterdam, Hong Kong, Qatar and Egypt also played a supporting role in confirming the biologic impact of the mutation in the VARS gene.
Advertisements
"Such cooperation and patient matching plays a critical role in the identification of new genes and provision of diagnoses to geographically dispersed individuals with the same rare disorder," Dr. Friedman said.
In future experiments, the researchers hope to test whether dietary supplementation with valine or gene therapy may help to restore the altered protein in the brain of these children.
Source-Eurekalert