Tadpoles have helped researchers identify a new genetic disease that affects children's brain development.
The condition is so new it doesn’t have a name yet. It causes some children’s brains to develop abnormally. This results in delayed intellectual development. Most patients with it have severe learning difficulties which affect their quality of life.
Proving which gene causes the disease
One in 17 people will suffer from a rare disease at some time in their lives. Most of these rare diseases have a genetic cause and often affect children. Yet proving which gene change causes a disease is a huge challenge.
The research was led by a team from the universities of Southampton, Portsmouth and Copenhagen, including the Wessex Clinical Genetics Service at University Hospital Southampton. They found changes in a gene called Glutamate Ionotropic Receptor AMPA Type Subunit 1 (GRIA1) caused this rare disease.
This discovery will help doctors develop targeted treatments for patients and their families. It will also open the door to screening and diagnosis in pregnancy.
Changing the behaviour of tadpoles
Studies connecting a gene and a disease are usually done using mice. But several studies have recently shown that experiments in tadpoles can also provide very strong evidence about the function of variant human genes.
The GRIA1 gene helps to move electrical signals around the brain. If this process is interrupted or made less efficient, it can cause a reduction in the brain’s capacity to store information.
The team consisted of frog geneticists, biochemists and clinical geneticists. Using gene editing, they mimicked the human gene changes in tadpoles. They also did a biochemical analysis of the gene changes in frog eggs.
Together they showed these changes in GRIA1 are the underlying cause of this behaviour-altering disease. The results are published in the American Journal of Human Genetics.
Joint lead author Prof Diana Baralle, NIHR Southampton Biomedical Research Centre researcher, Professor of Genomic Medicine and Consultant in Clinical Genetics, said: “Discovering these new causes for genetic disorders ends our patients’ diagnostic odyssey. This has been made possible by collaborative interdisciplinary working across universities.”