Featured Research

from universities, journals, and other organizations

Three continents, one gene: DNA detectives track down nerve disorder cause

Date:
August 13, 2012
Source:
University of Michigan Health System
Summary:
A global hunt for the cause of a crippling inherited nerve disorder has found its target. The discovery opens the door for better diagnosis and treatment of this disease – but also for better understanding of why nerves in the brain’s movement-controlling center die, and how to find the causes of other diseases that run in families.

An image from the research, showing normal presence of the protein encoded by the gene at left, and much-reduced presence in cells with a mutated form of the gene.
Credit: Image courtesy of University of Michigan Health System

A global hunt for the cause of a crippling inherited nerve disorder has found its target. The discovery opens the door for better diagnosis and treatment of this particular disease -- but also for better understanding of why nerves in the brain's movement-controlling center die, and how new DNA-mapping techniques can find the causes of other diseases that run in families.

In a new paper in the Annals of Neurology, a team from Taiwan, France and the University of Michigan Health System report that mutations in the gene KCND3 were found in six families in Asia, Europe and the United States that have been haunted by the same form of a disease called spinocerebellar ataxia or SCA. The disease causes progressive loss of balance, muscle control and ability to walk.

The new paper finds the disease gene in a region of chromosome 1 where a Dutch group had previously shown linkage with a form of SCA called SCA19, and the Taiwanese group on the new paper had shown similar linkage in a family for a form of the disease that was then called SCA22.

The Dutch group has just published results in the same issue of the journal, zeroing in on the same gene as the U-M/Taiwanese/French groups.

The gene governs the production of a protein that allows nerve cells to "talk" to one another through the flow of potassium. Pinpointing its role as a cause of ataxia will now allow more people with ataxia to learn the exact cause of their disease, give a very specific target for new treatments, and perhaps allow the families to stop the disease from affecting future generations.

But the findings also have significance beyond ataxia. The researchers also show that when KCND3 is mutated, it causes not only poor communication between nerve cells in the cerebellum -- but also the death of those cells. It's information that could aid research on other neurological disorders involving balance and movement.

Margit Burmeister, Ph.D., the U-M geneticist who helped lead the work, notes that the gene could not have been found without a great deal of DNA detective work -- and the cooperation of the families who volunteered to let researchers map all the DNA of multiple members of their family tree.

"We combined traditional genetic linkage analysis in families with inherited diseases with whole exome sequencing of an individual's DNA, allowing us to narrow down and ultimately identify the mutation," she says. "This new type of approach has already resulted in many new gene identifications, and will bring in many more."

U-M neurologist Vikram Shakkottai, M.D., Ph.D., an ataxia specialist and co-author on the paper, notes that the new genetic information will help patients find out the specific cause of their disease -- a reassuring thing in itself.

But he and his colleagues are already working to find drugs that might alter potassium flow, and provide a treatment for a group of diseases that currently are only treated with supportive care such as physical activity and balance training as patients deteriorate.

"Many of the families who come to our clinic for treatment don't have a recognized genetic mutation, so it's important to find new genetic mutations to explain their symptoms," says Shakkottai, an assistant professor in the U-M Department of Neurology. "But at the same time, this research is helping us understand a common mechanism of nerve cell dysfunction in progressive and non-progressive disease."

Some forms of ataxia, called episodic, do not cause progressive worsening of symptoms -- but past research has shown potassium and calcium channel mutations to be at the root of them, too.

Burmeister is a member of the U-M Molecular & Behavioral Neuroscience Institute and a professor in the departments of Human Genetics, Computational Medicine & Bioinformatics and Psychiatry at the U-M Medical School. Jun Li, Ph.D., an assistant professor of human genetics and CMB, led the exome sequencing using the U-M Medical School's DNA Sequencing Core.

The U-M researchers worked with partners at the National Yang-Ming University School of Medicine in Taipei, Taiwan, and the Taipei Veterans General Hospital, as well as teams at the University of Tokyo and the Hopital Pitie-Salpetriere in Paris. Each center had identified one family that mapped near SCA19, previously also known as SCA22, and gotten their permission to study their DNA in depth.

The family studied at U-M is of Ashkenazi Jewish heritage, and Burmeister notes that other families of this background with unexplained ataxias may turn out to have the KCND3 mutation.

The Dutch team that is publishing its findings about KCND3 at the same time studied families in the Netherlands. They found that mutations on the gene are responsible for SCA 19, which until now had no specific cause known.

"In other words, mutations in this gene are not uncommon and present all over the world," says Burmeister. "This means that in the future, this gene should be tested for mutations as part of a clinical genetic test panel for patients with ataxia symptoms. Because a generation can be skipped, it may even be relevant in some sporadic cases -- those where the patient isn't aware of any other family members with a similar disease."

While a test is not quite available yet, it should be soon through testing laboratories that partner with clinics such as U-M's.

At the same time, families affected by ataxia who don't yet know the cause might be eligible to volunteer for U-M research.


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.


Journal Reference:

  1. Yi-chung Lee, Alexandra Durr, Karen Majczenko, Yen-hua Huang, Yu-chao Liu BS, Cheng-chang Lien, Pei-chien Tsai PhD, Yaeko Ichikawa, Jun Goto, Marie-Lorraine Monin, Jun Z. Li, Ming-yi Chung, Emeline Mundwiller, Vikram Shakkottai, Tze-tze Liu, Christelle Tesson, Yi-chun Lu, Alexis Brice, Shoji Tsuji, Margit Burmeister, Giovanni Stevanin, Bing-wen Soong. Mutations in KCND3 cause spinocerebellar ataxia type 22. Annals of Neurology, 2012; DOI: 10.1002/ana.23701

Cite This Page:

University of Michigan Health System. "Three continents, one gene: DNA detectives track down nerve disorder cause." ScienceDaily. ScienceDaily, 13 August 2012. <www.sciencedaily.com/releases/2012/08/120813103254.htm>.
University of Michigan Health System. (2012, August 13). Three continents, one gene: DNA detectives track down nerve disorder cause. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2012/08/120813103254.htm
University of Michigan Health System. "Three continents, one gene: DNA detectives track down nerve disorder cause." ScienceDaily. www.sciencedaily.com/releases/2012/08/120813103254.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. Video provided by Newsy
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