Featured Research

from universities, journals, and other organizations

Biology behind brain development disorder: Mutations in the gene, UBE3B, cause a rare genetic disorder in children

Date:
November 29, 2012
Source:
Wellcome Trust Sanger Institute
Summary:
A combination of sequencing and mouse models were used to identify the gene responsible for a brain developmental disorder seen in four patients. The study also shows that the biology uncovered in the mouse model helps to understand the symptoms in patients.

This study describes how a combination of sequencing and mouse models were used to identify the gene responsible for a brain developmental disorder seen in four patients. The study also shows that the biology uncovered in the mouse model helps to understand the symptoms in patients.

Related Articles


The work highlights how animal models are a complementary approach for determining the causal genes and for understanding the biology behind genetic disorders.

Researchers have defined the gene responsible for a rare developmental disorder in children. The team showed that rare variation in a gene involved in brain development causes the disorder. This is the first time that this gene, UBE3B, has been linked to a disease.

By using a combination of research in mice and sequencing the DNA of four patients with the disorder, the team showed that disruption of this gene causes symptoms including brain abnormalities and reduced growth, highlighting the power of mouse models for understanding the biology behind rare diseases.

"Ubiquitination, the biological pathway UBE3B is involved in, is crucial in neurodevelopment," says Dr Guntram Borck, lead author from the University of Ulm. "We have studied several patients with this rare condition, and by sequencing the coding regions of the genome of these patients we found mutations implicating the gene UBE3B. This result was confirmed by studies performed in mice by our collaborators at the Sanger Institute.

At the Sanger researchers deleted the gene in mice and found that they had symptoms that were quite similar to those in the patients with UBE3B mutations including; reduced body weight and size, and reduced size of the brain.

The studies in mice also uncovered other defects underlying the disorder. Mice with the gene deletion had reduced cholesterol levels, a symptom that was seen by the team in three of the patients. This observation suggests that a defect in cholesterol metabolism is associated with this syndrome.

"Both techniques, DNA sequencing and deleting the gene in mice, support the finding that disruption of UBE3B causes this syndrome," says Dr David Adams, lead author from the Wellcome Trust Sanger Institute. "We can now learn much more about this syndrome by studying these mice. They also represent a pre-clinical model in which we may trial potential new therapies.

"This is the first time that this gene has been implicated in any disorder."

DNA sequencing has greatly improved the identification of variants associated with developmental disorders. But the challenge still remains for researchers to identify which of these variants, there are usually several hundred identified in each patient, cause the disorder. Animal models are a complementary approach for determining the causal gene and for understanding the biology behind genetic disorders..

"The syndromes we are studying, although rare, tell us a huge amount about biology," says Dr Helen Firth, Consultant Clinical Geneticist at Cambridge Universities Hospital Trust. "Understanding the biology behind these disorders could improve our management of these rare conditions and provide new avenues of research into treatments for scientists to pursue."


Story Source:

The above story is based on materials provided by Wellcome Trust Sanger Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. Lina Basel-Vanagaite, Bruno Dallapiccola, Ramiro Ramirez-Solis et al. Deficiency for the Ubiquitin Ligase UBE3B in a Blepharophimosis-Ptosis-Intellectual Disability Syndrome. American Journal of Human Genetics, 29 Nov. 2012 DOI: 10.1016/j.ajhg.2012.10.011

Cite This Page:

Wellcome Trust Sanger Institute. "Biology behind brain development disorder: Mutations in the gene, UBE3B, cause a rare genetic disorder in children." ScienceDaily. ScienceDaily, 29 November 2012. <www.sciencedaily.com/releases/2012/11/121129130406.htm>.
Wellcome Trust Sanger Institute. (2012, November 29). Biology behind brain development disorder: Mutations in the gene, UBE3B, cause a rare genetic disorder in children. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/11/121129130406.htm
Wellcome Trust Sanger Institute. "Biology behind brain development disorder: Mutations in the gene, UBE3B, cause a rare genetic disorder in children." ScienceDaily. www.sciencedaily.com/releases/2012/11/121129130406.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins