Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene discovery aids understanding of common inherited neurological disorder

25.06.2007
Benefiting from Human Genome Project, University of Michigan scientists rapidly find mutation that causes one form of Charcot-Marie-Tooth disorder

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. This work now appears online ahead of print in the journal Nature.

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.

Anne Rueter | EurekAlert!
Further information:
http://www.charcot-marie-tooth.org

Further reports about: Discovery FIG4 Meisler Mutation U-M inherited neurological peripheral

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>