Featured Research

from universities, journals, and other organizations

Gene Discovery Aids Understanding Of Common Inherited Neurological Disorder

Date:
June 22, 2007
Source:
University of Michigan Health System
Summary:
Scientists have identified the gene responsible for one type of Charcot-Marie-Tooth disorder, a common inherited neurological disease, thanks to the chance appearance of a strain of impaired "pale tremor" mice in a research laboratory. Researchers tracked down the gene responsible for similar disability in people. Charcot-Marie-Tooth disorder causes leg pain, muscle weakness and foot deformities.

Scientists have identified the gene responsible for one type of Charcot-Marie-Tooth disorder, a common inherited neurological disease, thanks to the chance appearance of a strain of impaired "pale tremor" mice in a University of Michigan research laboratory.

The discovery of the gene mutation means a genetic test will be possible for people with a less common subtype of the disorder -- one that until now was unidentified and had an unknown genetic basis, says Miriam Meisler, senior author of the study.

Charcot-Marie-Tooth disorder, one of the most prevalent inherited neurological disorders, affects one in 2,500 people in the United States, usually beginning in youth or by mid-adulthood. It is actually a group of related disorders that affect the body's peripheral nerves, with symptoms such as pain and.muscle weakness in the feet and legs that lead to foot deformities, tripping and difficulty walking.

The gene abnormalities responsible for 70 percent of cases are already known. Those patients and their families can choose to have genetic tests, which may be used to guide treatment or help family members find out if they are at risk.

But the remaining 30 percent of patients, who have different variants of the disease, have not had that option. Meisler, a professor of human genetics at the U-M Medical School, predicts the new discovery will quickly lead to a test that can diagnose which of those patients have the newly identified gene mutation. These probably represent about 5 percent of the unexplained 30 percent of cases, preliminary testing suggests. With genetic knowledge, "Family members can make decisions about reproduction," Meisler says of the discovery's implications. "It also opens up directions for developing therapies. Now pharmacologists and drug developers can target this gene."

The genetic sleuthing that led to the discovery began when scientists in Meisler's genetics lab noticed that some mice of a common laboratory type gave birth to offspring with a strange, wobbly gait and light coat color. The offspring quickly developed signs of severe central nervous system degeneration and peripheral neuropathy and died. The team named the strain "pale tremor" mice for their lack of normal pigment and the severe trembling they developed soon after birth.

What could explain the mice's debilitating symptoms" And could that knowledge be relevant in people with neurological diseases" Clement Y. Chow, the study's lead author and a U-M Ph.D. student in human genetics, pursued answers.

Chow was able to identify the gene involved, called FIG4, and find the mutation responsible for the symptoms in less than three years. That's a third of the time it might have taken two decades ago, in part because of valuable data from the Human Genome Project, Meisler says.

Meisler's research team, which included scientists at the U-M Life Sciences Institute, found that the mutation caused a signaling molecule, called PI(3,5)P2, to be under-produced in both yeast and mice cells. This little-studied signaling molecule was known to be present in yeast cells but has not been well studied in mammals.

The researchers also identified how the loss of normal FIG4 gene function results in disease in the pale tremor mice: Large fluid-filled chambers called vacuoles crowd the nerve cells and disrupt cell processes.

"In mice, the peripheral nervous system was most affected. So we decided to ask whether human patients with peripheral neuropathic disease had the same mutation," says Meisler.

The researchers tested 95 patients with Charcot Marie Tooth disorder of unknown cause. In four patients, they found mutations of FIG4, the same gene implicated in the diseased mice. The finding has resulted in a newly identified form of the disease called CMT4J.

In the phase of the research involving human patients, the multidisciplinary team of U-M scientists collaborated with scientists at Wayne State University and Baylor College of Medicine in Houston.

The study also produced other intriguing findings:

  • The signaling function governed by the FIG4 gene, common to yeast, mice and humans, is what geneticists call a "conserved function," persisting since very early in evolution.
  • The pale tremor mouse will be useful as a laboratory animal model in further research on Charcot-Marie-Tooth disorder as well as other conditions involving neuropathy. Meisler's lab plans to use the mice in studies to find out why their neurons deteriorate so rapidly.

Journal Citation: "Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J,"Nature on-line, June 17, 2007, doi:10.1038/nature05876

In addition to Meisler and Chow, U-M contributors to the study include: Yanling Zhang, Natsuko Jin and Lois Weisman of the Life Sciences Institute; James Dowling of the Department of Neurology; and Maja Adamska of the Department of Human Genetics The research was funded by the National Institutes of Health.

Additional Information:

Patent protection has been applied for. The University of Michigan, through its Office of Technology Transfer, is looking for licensing partners to help bring the technology to market. At the time this research was published the test for the CMT4J mutation was not available for routine use in humans.


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Cite This Page:

University of Michigan Health System. "Gene Discovery Aids Understanding Of Common Inherited Neurological Disorder." ScienceDaily. ScienceDaily, 22 June 2007. <www.sciencedaily.com/releases/2007/06/070621102604.htm>.
University of Michigan Health System. (2007, June 22). Gene Discovery Aids Understanding Of Common Inherited Neurological Disorder. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2007/06/070621102604.htm
University of Michigan Health System. "Gene Discovery Aids Understanding Of Common Inherited Neurological Disorder." ScienceDaily. www.sciencedaily.com/releases/2007/06/070621102604.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) 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:
from the past week

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