'Brain-only' mutation causes epileptic brain size disorder

April 11, 2012

Scientists have discovered a mutation limited to brain tissue that causes hemimegalencephaly (HMG), a condition where one half of the brain is enlarged and dysfunctional, leading to intellectual disability and severe epilepsy. The research, published by Cell Press in the April 12 issue of Neuron, has broad significance as a potential model for other complex neuropsychiatric diseases that may also be caused by "brain-only" mutations.

Mutations can be inherited or occur spontaneously. Inherited mutations are present throughout all cells of the body, but some can occur during development and hence be limited to cells in some organs but not others. For some time it has been suspected that there might be neurological diseases that are caused by mutations limited to the brain, but this had not yet been definitively demonstrated as it is very difficult to study brain tissue.

"The striking asymmetry of the brain in individuals with HMG has long suggested that this disease may be caused by a spontaneous mutation restricted to one half of the brain and detectable by direct study of affected brain tissue," explains the study's first author, Dr. Ann Poduri, from Children's Hospital and Harvard Medical School.

Patients with HMG often have dozens of seizures per day, which so interferes with their cognitive development that doctors make the difficult decision to remove brain tissue in a desperate attempt to control the seizures. Fortunately, these operations are frequently successful in controlling seizures and allowing children to develop remarkably normally. Such operations provided brain tissue samples that were used by Dr. Poduri and her colleagues to identify mutations in the AKT3 gene in HMG brain tissue. Previous research has linked AKT3 with the control of . The AKT3 mutations were restricted to the affected brain tissue, and were not evident in , suggesting that the mutation was spontaneous and not inherited.

"Our data suggest that spontaneous mutations resulting in abnormal activation of AKT3 contribute to overgrowth of one-half of the brain. The size and architecture of HMG may be determined in part by the stage at which the mutation occurs relative to the stage of brain development," concludes senior study author, Dr. Christopher Walsh from Children's Hospital Boston, Howard Hughes Medical Institute, and Harvard Medical School. "It is also notable that, to our knowledge, this is the first disease attributed to mutations that are limited to . There are other epilepsies and that are associated with spontaneous mutations and are therefore also candidates for these sorts of 'brain-only' mutations."

The study was supported by the Howard Hughes Medical Institute, the National Institute of and Stroke, and the National Institute of Mental Health.

Explore further: How brain tumors invade

More information: Poduri et al.: “Somatic Activation of AKT3 Causes Hemispheric Developmental Brain Malformations.” DOI:10.1016/j.neuron.2012.03.010

Related Stories

How brain tumors invade

December 12, 2011

Scientists have pinpointed a protein that allows brains tumors to invade healthy brain tissue, according to work published this week in the Journal of Experimental Medicine.

Understanding Schizophrenia

November 16, 2011

(Medical Xpress) -- Genetic mutations that cause schizophrenia could be linked to systems in the brain responsible for learning and memory, a major University study suggests.

Recommended for you

Rat brain atlas provides MR images for stereotaxic surgery

October 21, 2016

Boris Odintsov, senior research scientist at the Biomedical Imaging Center at the Beckman Institute for Advanced Science and Technology at the University of Illinois in Urbana-Champaign, and Thomas Brozoski, research professor ...

ALS study reveals role of RNA-binding proteins

October 20, 2016

Although only 10 percent of amyotrophic lateral sclerosis (ALS) cases are hereditary, a significant number of them are caused by mutations that affect proteins that bind RNA, a type of genetic material. University of California ...

Imaging technique maps serotonin activity in living brains

October 20, 2016

Serotonin is a neurotransmitter that's partly responsible for feelings of happiness and for mood regulation in humans. This makes it a common target for antidepressants, which block serotonin from being reabsorbed by neurons ...

Overcoming egocentricity increases self-control

October 19, 2016

Neurobiological models of self-control usually focus on brain mechanisms involved in impulse control and emotion regulation. Recent research at the University of Zurich shows that the mechanism for overcoming egocentricity ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.