Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene discovery aids understanding of common inherited neurological disorder

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:

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

More articles from Life Sciences:

nachricht Molecular doorstop could be key to new tuberculosis drugs
20.03.2018 | Rockefeller University

nachricht Modified biomaterials self-assemble on temperature cues
20.03.2018 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Mars' oceans formed early, possibly aided by massive volcanic eruptions

20.03.2018 | Physics and Astronomy

Thawing permafrost produces more methane than expected

20.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>