Featured Research

from universities, journals, and other organizations

Mutation location is the key to prognosis

Date:
February 28, 2013
Source:
Baylor College of Medicine
Summary:
The three most important factors in real estate are location, location, location, and the same might be said for mutations in the gene MECP2, researchers report in a new study.

The three most important factors in real estate are location, location, location, and the same might be said for mutations in the gene MECP2, said researchers at Baylor College of Medicine and the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital in a report in the journal Cell.

Related Articles


"Where a mutation occurs can affect the severity of the symptoms of the disease," said Dr. Huda Zoghbi, professor of molecular and human genetics at BCM and director of the NRI. Zoghbi, corresponding author of the report, found the MECP2 gene in 1999 and confirmed that deficiency in the protein causes Rett syndrome, a post natal genetic disease that mainly affects girls.

Symptoms influenced by gene location

In the study, she and her colleagues relied on data from rare male patients with disruptions in MECP2 that showed that severity of symptoms could be influenced by the location of the gene mutation. The few boys with this disorder fell into two broad categories: Those who suffered severe brain disease and death before age 4 and those who lived for decades with symptoms similar to that of Rett or developmental delay and other disorders similar to those seen in autism.

Looking at the placement of the mutations in the boys, they hypothesized there was a distinct difference in symptoms seen in boys who had mutations at amino acid 270 in the protein and those who had mutations only slightly farther along, at amino acid 273. The protein is truncated or shorter in those with amino acid 270 mutations than those with the mutation at amino acid 273.

After Steven Baker, a graduate student in the Program in Developmental Biology at BCM, generated and characterized mice that had mutations at the two sites of the protein, he found that mice who had mutations at amino acid 273 lived longer and developed symptoms later than those mice who had mutations at amino acid 270 or those who lacked the MeCP2 protein all together (knock-out mice).

Disruption of topological feature

One reason for the differences could be that the mutation at amino acid 270 disrupts a key topological feature of the DNA -- an AT-Hook domain that is a DNA binding motif. By disrupting this domain, the mutation could affect the way the protein bind the DNA and make the already truncated protein much less effective.

"The participation of patients and their families with Rett researchers really helped us to key in on regions of MeCP2 that are critical for its function," said Baker, who is also an M.D./Ph.D. student in BCM's Medical Student Training Program.

The researchers propose a model for this DNA binding in which MeCP2 binds to sites across the genome. In some spots where this occurs, the protein manipulates the structure of the nearby chromatin.

Chromatin architectural factor

"We think that one function of MeCP2 (the protein associated with the gene) is to alter the architecture of chromatin (the mass of proteins and DNA found in the nucleus of the cell)," said Zoghbi, who is also Howard Hughes Medical Institute investigator.

Baker said, "The picture of MeCP2 as a chromatin architectural factor is emerging from the combined efforts of many laboratories. Understanding how MeCP2 modifies chromatin structure will ultimately allow us to understand why it is so important for neuronal health."

Others who took part in this work include Lin Chen, Angela Dawn Wilkins, Peng Yu and Olivier Lichtarge, all of BCM.

Funding for this work came from the Howard Hughes Medical Institute, the National Institute of Neurological Disease and Stroke (HD053862), and the Baylor College of Medicine Intellectual and Developmental Disability Research Center (F30NS066527).


Story Source:

The above story is based on materials provided by Baylor College of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Steven Andrew Baker, Lin Chen, Angela Dawn Wilkins, Peng Yu, Olivier Lichtarge, Huda Yahya Zoghbi. An AT-Hook Domain in MeCP2 Determines the Clinical Course of Rett Syndrome and Related Disorders. Cell, 2013; 152 (5): 984 DOI: 10.1016/j.cell.2013.01.038

Cite This Page:

Baylor College of Medicine. "Mutation location is the key to prognosis." ScienceDaily. ScienceDaily, 28 February 2013. <www.sciencedaily.com/releases/2013/02/130228124130.htm>.
Baylor College of Medicine. (2013, February 28). Mutation location is the key to prognosis. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2013/02/130228124130.htm
Baylor College of Medicine. "Mutation location is the key to prognosis." ScienceDaily. www.sciencedaily.com/releases/2013/02/130228124130.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Rural India's Low-Cost Sanitary Pad Revolution

Rural India's Low-Cost Sanitary Pad Revolution

AFP (Nov. 28, 2014) — One man hopes his invention -– a machine that produces cheap sanitary pads –- will help empower Indian women. Duration: 01:51 Video provided by AFP
Powered by NewsLook.com
Research on Bats Could Help Develop Drugs Against Ebola

Research on Bats Could Help Develop Drugs Against Ebola

AFP (Nov. 28, 2014) — In Africa's only biosafety level 4 laboratory, scientists have been carrying out experiments on bats to understand how virus like Ebola are being transmitted, and how some of them resist to it. Duration: 01:18 Video provided by AFP
Powered by NewsLook.com
WHO Says Male Ebola Survivors Should Abstain From Sex

WHO Says Male Ebola Survivors Should Abstain From Sex

Newsy (Nov. 28, 2014) — WHO cites four studies that say Ebola can still be detected in semen up to 82 days after the onset of symptoms. Video provided by Newsy
Powered by NewsLook.com
Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
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