Navigation Links
Potassium channel gene modifies risk for epilepsy
Date:4/4/2011

Vanderbilt University researchers have identified a new gene that can influence a person's risk for developing epilepsy. The findings, reported in the March 29 Proceedings of the National Academy of Sciences, could improve molecular diagnostic tools and point to novel therapeutic targets for epilepsy.

The gene, KCNV2, codes for a unique type of potassium channel, a protein that participates in the electrical activity of nerve cells. Disturbed electrical activity in the brain and resulting seizures are hallmarks of epilepsy, a group of disorders that affects about 1 percent of the world's population.

A number of genetic mutations that cause inherited epilepsies have been identified. But the clinical severity of inherited epilepsies varies widely from mild childhood seizures that resolve with age to severe lifelong seizures even in individuals who have the same single-gene mutation, said Jennifer Kearney, Ph.D., assistant professor of Medicine in the Division of Genetic Medicine.

The range of clinical severity "tells us that there are other factors that contribute," she said. "We think that susceptibility and resistance genes that are inherited in addition to the primary mutation are probably a major factor."

Identifying susceptibility and resistance genes may suggest new targets for drugs that fine-tune neuronal excitability, rather than dampening it completely as many current antiepileptic drugs do, Kearney said.

The investigators began to look for these types of "modifier" genes after they made a curious observation in a mouse model of epilepsy that epilepsy severity depended on the genetic background strain of the mice.

They were studying mice with an epilepsy-causing gene mutation in a sodium channel, a protein that is important for neuronal excitability. The mice had spontaneous, progressive seizures and a reduced lifespan. But when the researchers "moved" the gene mutation into mice with a different genetic background (using breeding strategies), the epilepsy became less severe: the mice developed seizures later and had improved survival.

Using genetic strategies, the investigators zeroed in on two chromosome regions that influenced the difference in epilepsy severity in the two mouse strains. In one of these regions, the mouse Kcnv2 gene (the mouse equivalent of the human KCNV2 gene) appeared to be the strongest candidate gene, based on its potential for altering electrical activity in neurons.

The current report demonstrates that increased expression of the mouse Kcnv2 gene not changes in its coding sequence is associated with more severe epilepsy in the susceptible mouse strain. Increasing Kcnv2 expression in the resistant mouse strain caused these mice to develop more severe symptoms, supporting the gene's contribution as an epilepsy modifier.

The investigators then screened 209 pediatric epilepsy patients for variations in KCNV2 and found two different variations in two unrelated patients.

Colleagues in the laboratory of Alfred George Jr., M.D., director of the Division of Genetic Medicine, conducted electrophysiology studies in cells to examine how the two variations affected the function of the potassium channel. They found that both variations suppressed a type of potassium current that normally dampens excitability in neurons.

"The mutations make a neuron more excitable, so you could have longer periods of excitation and also repetitive excitation (that leads to seizures)," Kearney said.

The team plans to screen additional patients with epilepsy to assess the incidence of variations in KCNV2. They are also collaborating with Dave Weaver, Ph.D., director of the Vanderbilt High-Throughput Screening Facility, to find compounds that target the potassium channel and may be useful therapeutics for epilepsy.

Kearney said that understanding how genes such as KCNV2 modify the clinical severity of epilepsy is important for molecular diagnostics and genetic counseling. Patients may currently learn that they have an epilepsy-causing gene mutation, but because clinical severity varies, their prognosis may not be clear.

"We need to understand how all of these different gene interactions impact the final clinical disorder to improve risk assessment and disease management in epilepsy," Kearney said.


'/>"/>

Contact: Leigh MacMillan
leigh.macmillan@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
Source:Eurekalert  

Related biology news :

1. Flow of potassium into cells implicated in schizophrenia
2. Advance in microchannel manufacturing opens new industry applications
3. K-State research channels powerful Kansas wind to keep electricity running
4. Polymer membranes with molecular-sized channels that assemble themselves
5. Tiny channels carry big information
6. Solving the puzzle of the BK ion channel
7. Chloride channels render nerve cells more excitable
8. A lab-on-a-chip with moveable channels
9. New studies reveal downstream processes of ion channel inactivation
10. MDC researchers develop new tool to investigate ion channels
11. Nervy research: Researchers take initial look at ion channels in a model system
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Potassium channel gene modifies risk for epilepsy
(Date:2/1/2016)... NEW YORK , Feb. 1, 2016  Today, ... Heart Association (AHA) announced plans to develop a first ... cognitive computing power of IBM Watson. In the first ... disease, AHA, IBM (NYSE: IBM ), and Welltok ... metrics and health assessments with cognitive analytics, delivered on ...
(Date:1/25/2016)... Jan. 25, 2016  Glencoe Software, the world-leading supplier ... publication industries, will provide the data management solution OMERO ... Photo ... Phenotypic analysis measures the characteristics ... allowing comparisons between states such as health and disease, ...
(Date:1/20/2016)... --  MedNet Solutions , an innovative SaaS-based eClinical technology ... is pleased to announce the attainment of record-setting corporate ... of the company,s laser focus on (and growing international ... comprehensive, easy-to-use and highly affordable cloud-based technology platform. ... growth achievements in 2015 include: , Record ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... 2016 ASAE is introducing a hybrid membership ... (AMC) the option of joining or renewing through an ... by staff size, every employee in any size association ... reap all available member benefits.   John ... membership options will allow organizations of any size and ...
(Date:2/10/2016)... , Feb. 10, 2016  Allergan plc (NYSE: ... announced that Brent Saunders , Allergan,s CEO and ... a fireside chat session at the RBC Capital Markets ... p.m. ET at The New York Palace Hotel in ... will be webcast live and can be accessed on ...
(Date:2/10/2016)... ... February 10, 2016 , ... HOLLOWAY ... of Pharmaceutical Engineering (ISPE) Rocky Mountain Chapter 21st Annual Vendor Exhibition on Thursday, ... more than 100 tables for its annual event, which will run from 3:00 ...
(Date:2/10/2016)... CA (PRWEB) , ... February 10, 2016 , ... ... Multiplex Testing (PROMPT), a research registry built on the secure online PatientCrossroads platform, ... 2014. More than 1,600 participants have joined the PROMPT study, which seeks to ...
Breaking Biology Technology: