Featured Research

from universities, journals, and other organizations

With Just Three Affected Individuals, Researchers Find Gene Behind Rare Form Of Epilepsy

Date:
March 3, 2008
Source:
Cell Press
Summary:
Researchers have found a gene responsible for a particularly debilitating form of epilepsy that also leads to kidney failure. Epilepsy is overall a common condition, affecting some two percent of people. The genetics behind the seizure disorder are often complex. However, progressive myoclonus epilepsies, which Berkovic said can be quite disabling and tend to get worse over time, usually have a simpler, Mendelian pattern of inheritance caused by a variety of single genes.

Researchers have found a gene responsible for a particularly debilitating form of epilepsy that also leads to kidney failure, according to a new article. What's more, the new findings, which begin to "crack open the cell biology of the problem," were made with the help of just three affected individuals.

"Many people will not have heard of this extraordinarily rare disease," said Samuel Berkovic of the University of Melbourne in Australia. "Nonetheless, the findings speak to the power of genetics to solve even quite rare problems."

Epilepsy is overall a common condition, affecting some two percent of people. The genetics behind the seizure disorder are often complex. However, progressive myoclonus epilepsies, which Berkovic said can be quite disabling and tend to get worse over time, usually have a simpler, Mendelian pattern of inheritance caused by a variety of single genes.

Action myoclonus-renal failure (AMRF) syndrome is a lethal inherited form of progressive myoclonus epilepsy associated with kidney failure. Symptoms usually arise when people reach the age of 15--25 with signs of kidney trouble or neurological symptoms including tremors, seizures, and later other movement disorders. Upon close inspection, the kidneys of those with AMRF show scarring, and their brains show an unusual buildup of storage material.

"The recessive gene defect underlying AMRF was unknown and the lack of large pedigrees and lethality of the disorder precluded a conventional mapping strategy," Berkovic said. So, his team came up with a new one.

The researchers first identified three unrelated families, each with a member having AMRF. They then used a modified version of "homozygosity mapping" to narrow the candidate regions of the genome down to places where both copies of a gene were identical in one inbred family, and they used affected and unaffected family members to narrow the hunt further. That exercise suggested that the gene involved could be found in a region on chromosome 4.

Then, they took another "quick shortcut" to finding the culprit, Berkovic said. Using microarray analysis, which measures gene expression, they identified genes within the implicated region that were turned down in those with AMRF.

That led them to SCARB2/Limp2as the likely candidate. Indeed, they showed, all of the families under study carried a mutation in the SCARB2/Limp2gene, which the researchers confirmed in two other unrelated AMRF families.

SCARB2/Limp2is active in a wide range of tissues, earlier studies had shown, where it is found on the surface of cellular components called lysosomes. Lysosomes play an important role inside of cells in breaking down spent parts, a process known as autophagy.

As luck would have it, mice lacking the gene had already been developed. Upon examination of those animals, the investigators found inclusions in the animals' brains and subtle abnormalities in their kidneys, reminiscent of people with AMRF.

Although further study is needed to work out exactly what happens in the brain and kidneys of people lacking this lysosomal gene, Berkovic said they do have some ideas.

"SCARB2/Limp2 might have a role in physiological autophagy and its deficiency could thus lead to accumulation of normally recycled proteins or organelles manifesting as inclusions [in the brain]," the researchers said.

On top of the insights into AMRF, the team's newly developed method might unlock other rare disorders.

"The whole trick is to exploit the particular family structure of affected and unaffected individuals," Berkovic said. "This strategy may be more widely applicable to the still many rare, Mendelian disorders yet to be solved."

Journal reference: Berkovic et al.: "Array based gene discovery with 3 unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis." The American Journal of Human Genetics (2008), March 2008 (online February 28).


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "With Just Three Affected Individuals, Researchers Find Gene Behind Rare Form Of Epilepsy." ScienceDaily. ScienceDaily, 3 March 2008. <www.sciencedaily.com/releases/2008/02/080228124412.htm>.
Cell Press. (2008, March 3). With Just Three Affected Individuals, Researchers Find Gene Behind Rare Form Of Epilepsy. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2008/02/080228124412.htm
Cell Press. "With Just Three Affected Individuals, Researchers Find Gene Behind Rare Form Of Epilepsy." ScienceDaily. www.sciencedaily.com/releases/2008/02/080228124412.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 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