A newly discovered neurodevelopmental disorder causes atypical brain growth and delayed intellectual growth, and it is so new it hasn’t even been named yet. The rare genetic disorder is thought to be caused by mutations in a protein-coding gene for an important neurotransmitter receptor, and people affected by it often have significant cognitive impacts.
The disorder is outlined in a new study published in the American Journal of Human Genetics.
Neurodevelopmental disorders, in an array of forms, affect around 1-3 percent of the Western population. It is thought that some of these disorders stem from just a single mutated gene involved in passing signals within the brain. One such set of receptors – Glutamate Ionotropic Receptor AMPA (GRIA) Types 2, 3 and 4 – have all been implicated in disease previously. GRIA Type 1 (GRIA1) is involved in the movement of electrical signals through the brain, and without it, the brain has difficulty remembering information. Now, new research suggests that GRIA1 mutations may result in a new type of disorder.
To identify just what this disorder is, researchers from Southampton, Portsmouth, and Copenhagen universities gathered a cohort of 5 subjects through a genomics database, all of which had similar symptoms, and another 2 people from alternative sources. All participants had mutations in GRIA1.
Genetic analysis of the participants highlighted multiple missense mutations of interest, plus a truncated mutation (produces a shorter protein).
The team then produced frog tadpoles with the GRIA1 gene knocked out to see what happens to development in its absence. They discovered the knockouts resulted in memory deficits in the tadpoles, plus stunted neurodevelopment. The results suggest that GRIA1 has large implications in brain development, which manifests itself into a previously-unknown disorder.
"This was a transformational piece of work for us; the ability to analyze human-like behaviors in tadpoles with sufficient accuracy to detect genetic disease-linked changes opens the opportunity to help identify a huge range of diseases. This is particularly important given that so many neurodevelopmental diseases are currently undiagnosed,” said Co-author Dr. Annie Goodwin in a statement.
“Discovering these new causes for genetic disorders ends our patients’ diagnostic odyssey and this has been made possible by collaborative interdisciplinary working across universities,” added Co-author Professor Diana Baralle.
The researchers are now looking to improve their process and develop new ways of treating these rare developmental disorders.