New brain development disorder identified by scientists

May 22, 2018, eLife
Credit: CC0 Public Domain

Researchers have identified a new inherited neurodevelopmental disease that causes slow growth, seizures and learning difficulties in humans.

Writing in the journal eLife, the team reveals that this disease is caused by a recessive mutation in CAMK2A—a gene that is well known for its role in regulating learning and memory in animals. The findings suggest that dysfunctional CAMK2 genes may contribute to other neurological disorders, such as epilepsy and autism, opening up potential new avenues for treating these conditions.

"A significant number of children are born with growth delays, neurological defects and intellectual disabilities every year across the world," explains senior author Bruno Reversade, Research Director at the Institute of Medical Biology and Institute of Molecular and Cell Biology, A*STAR, Singapore, who supervised the study. "While specific genetic have been identified for some patients, the cause remains unknown in many cases. Identifying novel mutations would not only advance our understanding of neurological diseases in general, but would also help clinicians diagnose children with similar symptoms and/or carry out genetic testing for expecting parents."

The team's research began when they identified a pair of siblings who demonstrated neurodevelopmental delay with frequent, unexplained seizures and convulsions. While the structure of their bodies developed normally, they did not gain the ability to walk or speak. "We believed that the children had novel mutations in CAMK2A, and we wanted to see if this were true," says Reversade.

The fully functional CAMK2A protein consists of multiple subunits. Using a genomic technique called exome sequencing, the team discovered a single coding error affecting a key residue in the CAMK2A gene that prevents its subunits from assembling correctly.

Moving their studies into the roundworm Caenorhabditis elegans, the scientists saw that this mutation disrupts the ability of CAMK2A to ensure proper neuronal communication and normal motor function. This suggests that the mutation is indeed the cause of the neurodevelopmental defects seen in the siblings.

To the best of the team's knowledge, this new disorder represents the first human disease caused by inherited mutations on both copies of the CAMK2A gene. In addition, another report* published recently identified single-copy mutations on both CAMK2A and CAMK2B that caused as soon as the mutations occurred. "We would like to bring these findings to the attention of those working in the area of paediatric genetics, such as clinicians and genetic counsellors, as there are likely more undiagnosed children with similar symptoms who have mutations in their CAMK2A gene," explains co-first author Franklin Zhong, Research Scientist in Reversade's lab at A*STAR.

"Neuroscientists working to understand childhood brain development, neuronal function and memory formation also need to consider this new disease, since CAMK2A is associated with these processes. In future, it would be interesting to test whether restoring CAMK2A activity can bring therapeutic benefit to patients with this condition, as well as those with related neurological disorders."

Explore further: The gene causing new brain disorder

More information: Poh Hui Chia et al, A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability, eLife (2018). DOI: 10.7554/eLife.32451

*Kury, S., van Woerden, G.M., Besnard, T., Proietti Onori, M., Latypova, X., Towne, M.C., Cho, M.T., Prescott, T.E., Ploeg, M.A., Sanders, S., et al. (2017). De Novo Mutations in Protein Kinase Genes CAMK2A and CAMK2B Cause Intellectual Disability. The American Journal of Human Genetics 101, 768-788.

Related Stories

The gene causing new brain disorder

March 23, 2018
Newly discovered gene mutations may help explain the cause of a disease that drastically impairs walking and thinking.

Mutation found in patients without a nose

September 15, 2017
A mutated gene in patients lacking a nose has been identified by an international team, a first step toward understanding nose development and possible therapies for another condition.

Newly identified gene mutation results in intellectual disability and developmental delay

April 12, 2018
An international group of researchers led by Cold Spring Harbor Laboratory (CSHL) Assistant Professor Gholson Lyon has identified a new genetic mutation associated with intellectual disability, developmental delay, autism ...

First 'non-gene' mutations behind neurodevelopmental disorders discovered

March 21, 2018
In the largest study of its kind, genetic changes causing neurodevelopmental disorders have been discovered by scientists at the Wellcome Sanger Institute and their collaborators in the NHS Regional Genetics services. The ...

Epileptic encephalopathy linked to protein trafficking gene

November 28, 2016
Researchers have linked a debilitating neurological disease in children to mutations in a gene that regulates neuronal development through control of protein movement within neuronal cells.

New neurodevelopmental syndrome identified

April 21, 2016
A multicenter research team led by Columbia University Medical Center (CUMC) has discovered a new neurodevelopmental syndrome and the genetic mutations that cause it. The discovery is an important step toward creating targeted ...

Recommended for you

A single missing gene leads to miscarriage

October 19, 2018
A single gene from the mother plays such a crucial role in the development of the placenta that its dysfunction leads to miscarriages. Researchers from the Medical Faculty of Ruhr-Universität Bochum (RUB) have observed this ...

Making gene therapy delivery safer and more efficient

October 18, 2018
Viral vectors used to deliver gene therapies undergo spontaneous changes during manufacturing which affects their structure and function, found researchers from the Perelman School of Medicine at the University of Pennsylvania ...

Student develops microfluidics device to help scientists identify early genetic markers of cancer

October 16, 2018
As anyone who has played "Where's Waldo" knows, searching for a single item in a landscape filled with a mélange of characters and objects can be a challenge. Chrissy O'Keefe, a Ph.D. student in the Department of Biomedical ...

Researchers use brain cells in a dish to study genetic origins of schizophrenia

October 16, 2018
A study in Biological Psychiatry has established a new analytical method for investigating the complex genetic origins of mental illnesses using brain cells that are grown in a dish from human embryonic stem cells. Researchers ...

Why heart contractions are weaker in those with hypertrophic cardiomyopathy

October 16, 2018
When a young athlete suddenly dies of a heart attack, chances are high that they suffer from familial hypertrophic cardiomyopathy (HCM). Itis the most common genetic heart disease in the US and affects an estimated 1 in 500 ...

Importance of cell cycle and cellular senescence in the placenta discovered

October 15, 2018
Working with researchers from Stanford University and St. Anna Children's Cancer Research, researchers from Jürgen Pollheimer's laboratory at the Medical University of Vienna's Department of Obstetrics and Gynecology have ...

0 comments

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.