Devastating disease that changes brain size discovered

September 7, 2017
Credit: University of Manchester

An international collaboration led by scientists and doctors from the UK, Netherlands and United States has identified a new genetic disease that affects the size of our brains and causes severe developmental problems.

While working on another project, Dr Siddharth Banka who is based at The University of Manchester and the Manchester Centre for Genomic Medicine, Saint Mary's Hospital, noticed three children with large or small brains, developmental delay and in a gene called RAC1.

At that point, it was difficult to be sure if it was a true finding, because RAC1 has never before been linked to human disease. And mutations in no other single gene have previously shown this extent of variability in brain-size.

As part of a parallel project, Professor Han Brunner and Dr Margot Reijnders of the Radboud University in Nijmegen had gathered together four more children with mutations in the same gene and altered brain-sizes. Some of the affected children were also found to have epilepsy and heart defects.

Dr Tom Millard also from The University of Manchester then used mouse cells to show that mutations in RAC1 affect the shape of the cells. When Dr Maria Kousi and Professor Nicholas Katsanis of Duke University, North Carolina found a similar effect of RAC1 mutations in brain-size of zebrafish, the team had no doubt they had discovered something new.

The study is published in the American Journal of Human Genetics.

"Evolution has tinkered with thousands of genes over millions of years, to shape the human brain, an organ that is remarkably consistent in its appearance and size across billions of people," said Dr Banka.

He added: "However, occasionally a tiny little alteration in just one of these thousands of can have devastating effects, reflecting the fine balance of this complex genetic orchestra."

Dr Reijnders said: "Remarkably, evolution has hardly meddled with RAC1. In fact, the RAC1 of the humble roundworm is not very different from the RAC1 present in your and my cells.

"This astonishing conservation across eons indicates the fundamental role of RAC1 in life. Hence, in some ways it is not surprising that a small alteration in this gene is difficult for us to tolerate."

Professor Han Brunner added: "These findings open new doors to our understanding of the development of the brain.

"We suspect RAC1 plays an important role in other genetic diseases as well".

Dr Banka added: "We are sure that this discovery will lead to identification of more patients with RAC1 mutations, who have not yet been diagnosed.

"The next step for the scientists will be to use this knowledge to work out possible treatments for this disease and related conditions."

Part of the study was based on the genetic data from the Wellcome Trust Sanger Institute in Cambridge.

The doctors and scientists who took part in this study are unable to deal with individual clinical enquires from the public. However, patients and families should in the first instance contact their GP who may refer them on to a local geneticist.

Explore further: Rac1 protein critical for lung development

Related Stories

Rac1 protein critical for lung development

October 20, 2016
A study by researchers from The Saban Research Institute of Children's Hospital Los Angeles reveals a promising therapeutic target for improving lung function in infants. Their study, now published online by the American ...

Identified the mechanism that controls localization of protein Rac1 in the cell nucleus

January 29, 2015
The sustained presence in the nucleus of the protein known as Rac1 produces changes in nuclear morphology that are important in several biological processes, including malignant cancer. This is the finding of the research ...

Post-breastfeeding tissue remodeling explained by new research

October 12, 2016
A ground-breaking study into the changes that occur in a woman's breast, from growing into one that provides milk for a new-born, and then back to its normal state, has discovered that milk-producing cells are, in effect, ...

Microcephaly brain size linked to mutation in stem cell micro environment

August 9, 2017
New research highlights the significant role the surrounding environment of stem cells, known as the niche, might play in the brain size of babies with microcephaly.

Possible psoriasis drug target identified

June 13, 2016
Psoriasis is one of the most common human skin diseases. People with severe cases sometimes resort to immunosuppressive treatment to quell the skin scaling, itching and joint arthritis that are hallmarks of the disorder. ...

Research findings could lead to new treatments for chronic inflammatory pain

February 10, 2016
New research uncovers a cascade of reactions within nerve cells that relay sensations of pain associated with inflammation. The findings, which are published in the British Journal of Pharmacology, indicate that drugs designed ...

Recommended for you

Genome editing enhances T-cells for cancer immunotherapy

November 20, 2017
Researchers at Cardiff University have found a way to boost the cancer-destroying ability of the immune system's T-cells, offering new hope in the fight against a wide range of cancers.

A math concept from the engineering world points to a way of making massive transcriptome studies more efficient

November 17, 2017
To most people, data compression refers to shrinking existing data—say from a song or picture's raw digital recording—by removing some data, but not so much as to render it unrecognizable (think MP3 or JPEG files). Now, ...

US scientists try first gene editing in the body

November 15, 2017
Scientists for the first time have tried editing a gene inside the body in a bold attempt to permanently change a person's DNA to try to cure a disease.

Genetic mutation in extended Amish family in Indiana protects against aging and increases longevity (Update)

November 15, 2017
The first genetic mutation that appears to protect against multiple aspects of biological aging in humans has been discovered in an extended family of Old Order Amish living in the vicinity of Berne, Indiana, report Northwestern ...

Genetic variant prompts cells to store fat, fueling obesity

November 13, 2017
Obesity is often attributed to a simple equation: People are eating too much and exercising too little. But evidence is growing that at least some of the weight gain that plagues modern humans is predetermined. New research ...

Discovering a protein's role in gene expression

November 10, 2017
Northwestern Medicine scientists have discovered that a protein called BRWD2/PHIP binds to histone lysine 4 (H3K4) methylation—a key molecular event that influences gene expression—and demonstrated that it does so via ...

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.