New research reveals gene mutation links to epilepsy and learning disabilities in children

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Research by Swansea University academics and Seattle Children’s Research Institute has identified a new gene which affects brain development and could cause epilepsy and learning disabilities in children.

Neurology and molecular neuroscience researchers at the University’s College of Medicine, led by Professor Mark Rees, the Center for Neural Development and Disease at the University of Rochester Medical Center, and Seattle Children’s Research Institute worked as part of an international multidisciplinary team on the research, which is published in the American Journal of Human Genetics (Cell Press Journal).

The researchers found the new gene can disrupt in utero and neonatal brain development resulting in children developing untreatable epilepsy or learning disabilities.  These are almost exclusively non-hereditary genetic disorders and the children affected would often need continuous care throughout their life.

The Swansea team were first contacted after genetic testing on two children with epilepsy by the University of Rochester and Seattle Children’s Research Institute. The tests revealed two mutations to the TUBBA2A gene that were not inherited from their parents, but occurred during development before birth and represented a new gene linked to malformations of the brain.

Using specialist neuroscience techniques and molecular modelling, Dr Thomas Cushion and Professor Mark Rees carried out an in-depth analysis of the mutation at Swansea University. Their tests confirmed that the mutations affect tubulin, which is a protein which drives brain development at the embryo and foetal stage.

Professor Mark ReesExplaining the importance of their findings, Professor Rees said: ‘Finding new genes in severe epilepsy disorders is a clinical and biomedical priority. It helps us to understand the mechanism of disease and once you have the mechanism you have a strategic advantage in designing and using new and established interventions. We are delighted to work with colleagues in the U.S.  to provide a pipeline of research that makes a difference to patients, parents and carers.’

Collaboration with Rochester and Seattle centres was instrumental to the outcomes of the study and Professor Dobyns at the Seattle Children’s Research Institute stated that: ‘First and foremost, this study provided a genetic diagnosis for both patients and their families. In addition, as both mutations were non-hereditary, it reassured parents that further offspring were at no increased risk of suffering from similar disorders. In the clinical domain, this study was important as it identified a new gene in the diagnosis of congenital malformations of the brain and cerebral cortex, as well as epilepsies.’

Now the team are considering looking for TUBB2A mutations in a larger cohort of patients, either with similar unexplained brain abnormalities and/or infantile epileptic seizures. If more cases are studied, it may be possible to define the characteristic TUBB2A-specific clinical features, to help future diagnoses and referrals for TUBB2A gene testing. There is also the possibility of further research into intervention testing.

Picture: Professor Mark Rees