Navigation Links
Gene discovery set to help with mysterious paralysis of childhood
Date:7/29/2012

DURHAM, N.C. Alternating hemiplegia of childhood (AHC) is a very rare disorder that causes paralysis that freezes one side of the body and then the other in devastating bouts that arise at unpredictable intervals. Seizures, learning disabilities and difficulty walking are common among patients with this diagnosis.

Researchers at Duke University Medical Center have now discovered that mutations in one gene cause the disease in the majority of patients with a diagnosis of AHC, and because of the root problem they discovered, a treatment may become possible.

The study was published online on July 29 in Nature Genetics.

AHC is almost always a sporadic disease, which means that typically no one else in the family has the disease, said Erin Heinzen, Ph.D., co-author of the study and Assistant Professor of Medicine in the Section of Medical Genetics. "Knowing that we were looking for genetic mutations in children with this disease that were absent in the healthy parents, we carefully compared the genomes of seven AHC patients and their unaffected parents. When we found new mutations in all seven children in the same gene we knew we had found the cause of this disease."

All of the mutations were found in a gene that encodes ATP1A3, one piece of a key transporter molecule that normally would move sodium and potassium ions across a channel between neurons (nerve cells) to regulate brain activity.

In a remarkably broad international collaborative effort, the authors partnered with three family foundations (USA, Italy and France), including scientists from 13 different countries, to study an additional 95 patients and showed over 75 percent had disease-causing mutations in the gene for ATP1A3.

"This study is an excellent example of how genetic research conducted on a world-wide scale really can make a difference for such a rare disorder as AHC," said Arn van den Maagdenberg, Ph.D., and co-author on the study and geneticist from Leiden University Medical Centre in the Netherlands. "It truly was an effort from many research groups that led to this remarkable discovery."

"This kind of discovery really brings home just what the human genome project and next-generation sequencing have made possible," said David Goldstein, Ph.D., Director of the Duke Center for Human Genome Variation and co-senior author on the study. "For a disease like this one with virtually no large families to study, it would have been very difficult to find the gene before next-generation sequencing."

"Ideally what you want from a study like this is a clear indication of how the mutations change protein function so you know how to screen for drugs that will restore normal function or compensate for the dysfunction," said Goldstein, who is also a Professor in Duke Molecular Genetics and Microbiology. "While there is considerably more work to do, our initial evaluation of the mutations suggests that they may alter the behavior of the transporter pump as opposed to reducing its activity, as do other mutations in the gene that cause a less severe neurological disease."

Co-senior author Mohamad Mikati, M.D., Professor of Pediatrics and of Neurobiology, and Chief of Pediatric Neurology at Duke, said, "Many years ago my work with other collaborators on a family with this disease proved that AHC can be caused by genetic factors, but until now we did not know the underlying gene abnormality.

"The finding that ATP1A3 mutations cause AHC will increase awareness of the disease and the ability to accurately diagnose patients," Mikati said. "While it may take a while for novel drugs to be developed to better treat this disease, we will see an immediate impact through specific testing for mutations in this gene when we suspect a case of AHC. This direct testing will prevent misdiagnoses that too often have caused patients to be treated with inappropriate medications."


'/>"/>

Contact: Mary Jane Gore
mary.gore@duke.edu
919-660-1309
Duke University Medical Center
Source:Eurekalert

Related biology news :

1. 3-D tumor models improve drug discovery success rate
2. OHSU discovery may lead to new treatment for ALS
3. Groundbreaking discovery of mechanism that controls obesity, atherosclerosis
4. Discovery may lead to new tomato varieties with vintage flavor and quality
5. 7 pharmaceutical companies join academic researchers to speed TB drug discovery
6. Discovery increases understanding how bacteria spread: U of A study
7. NSF Leadership in Discovery and Innovation sparks White House US Ignite Initiative
8. Groundbreaking discovery of the cellular origin of cervical cancer
9. Astellas and DNDi to collaborate on new drug discovery research for the treatment of NTDs
10. New discovery provides insight on long-standing pregnancy mystery
11. Speeding up drug discovery with rapid 3-D mapping of proteins
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/21/2016)... 21, 2016 NuData Security announced today that ... of principal product architect and that Jon ... customer development. Both will report directly to ... moves reflect NuData,s strategic growth in its product ... customer demand and customer focus values. ...
(Date:6/15/2016)... York , June 15, 2016 ... new market report titled "Gesture Recognition Market by Application ... Forecast, 2016 - 2024". According to the report, the  ... 11.60 billion in 2015 and is estimated to ... USD 48.56 billion by 2024.  Increasing ...
(Date:6/7/2016)... 7, 2016  Syngrafii Inc. and San Antonio ... that includes integrating Syngrafii,s patented LongPen™ eSignature "Wet" ... collaboration will result in greater convenience for SACU ... while maintaining existing document workflow and compliance requirements. ... Highlights: ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... June 27, 2016  Global demand for enzymes ... through 2020 to $7.2 billion.  This market includes ... cleaning products, biofuel production, animal feed, and other ... and biocatalysts). Food and beverages will remain the ... increasing consumption of products containing enzymes in developing ...
(Date:6/27/2016)... 27, 2016  Sequenom, Inc. (NASDAQ: SQNM ... lives through the development of innovative products and services, ... the United States denied its petition to ... of Sequenom,s U.S. Patent No. 6,258,540 (",540 Patent") are ... by the Supreme Court,s Mayo Collaborative Services v. Prometheus ...
(Date:6/27/2016)... ... June 27, 2016 , ... Parallel 6 , the leading software ... Clinical Reach Virtual Patient Encounter CONSULT module which enables both audio and ... clinical trial team. , Using the CONSULT module, patients and physicians can schedule a ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... will join the faculty of the University of North Carolina Kenan-Flagler Business ... strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s international ...
Breaking Biology Technology: