Navigation Links
Rare disease in Amish children sheds light on common neurological disorders
Date:5/11/2010

PHILADELPHIA So often the rare informs the common. Penn researchers investigating a regulatory protein involved in a rare genetic disease have shown that it may be related to epileptic and autistic symptoms in other more common neurological disorders.

A team of researchers from the University of Pennsylvania School of Medicine, led by Peter B. Crino, MD, PhD, associate professor of Neurology and director of the Penn Epilepsy Center, demonstrate how mutations in the STRAD-alpha gene can cause a disease called PMSE (polyhydramnios, megalencephaly, and symptomatic epilepsy) syndrome, found in a handful of Amish children. PMSE is characterized by an abnormally large brain, cognitive disability, and severe, treatment-resistant epilepsy.

Specifically, in an animal model, they found that the lack of the STRAD-alpha protein due to genetic mutations causes activation of the signaling pathway involving another protein called mTOR. In humans, this in turn may promote abnormal cell growth and cognitive problems in the developing brains of children. STRAD-alpha and mTOR proteins are part of a complex molecular network implicated in other, more common neurological disorders, many of which have autism-like symptoms as a component.

"The identification of a new gene that regulates mTOR provides fascinating insights into how mTOR pathway dysfunction may be associated with neurological disorders," says Crino. "Each new mTOR regulatory protein that is identified provides a new possible therapeutic target for drug development and treatment."

The research on PMSE published this month in the Journal of Clinical Investigation reveals clues about more common neurological disorders characterized by benign tumors and malformations of the brain, the most common of which is tuberous sclerosis complex (TSC). The root cause of TSC also lies in mutations in proteins along the mTOR pathway, however a different protein is affected compared to PMSE.

"It is quite compelling that TSC, a relatively common disorder, and PMSE, a rare disorder, are linked by a common cellular pathway, and exhibit similar severe neurological features," notes Crino. "In our study, we found that we could reverse some of the cellular features that result from STRAD-alpha deficiency in cell culture models of PMSE. This provides important conceptual support for more widespread treatment approaches that modify mTOR signaling in neurological disorders associated with epilepsy, autism, and cognitive disability."

Current estimates place tuberous sclerosis complex-affected births at one in 6,000. Nearly 1 million people worldwide are known to have TSC, with approximately 50,000 in the United States.

PMSE, on the other had, has only been described in 25 people in Lancaster County, PA. It's incidence among other Amish populations, let alone the rest of the country, is unknown. PMSE is also known as pretzel syndrome in the Amish community, because the lax joints of patients fold over easily. PMSE was identified in an Amish, or Old Order Mennonite pediatric population in 2007 by researchers from Penn and the Clinic for Special Children in Lancaster, PA, a genetic clinic devoted to the needs of the Amish.

The mTOR pathway normally controls cell growth, but in PMSE uncontrolled mTOR signaling leads to increases in brain size and areas in which the cerebral cortex is malformed. To prove this, the researchers knocked down the activity of the STRAD-alpha protein in a mouse model and caused malformations of the developing brain. The structure of these malformations was similar to what is seen in human PMSE and TSC and supports the conclusion that normal brain development in part depends on normal STRAD-alpha function. Localized brain malformations are among the most common causes of epilepsy and neurological disability in children.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. Proper Foot Care a Must for Patients with Peripheral Arterial Disease
2. Air Pollution Raises Risk of Heart Disease, Death
3. Genes Tie Blood Fat to Heart Disease
4. Same disease, different stem cell models
5. MU awarded $8.5 million to explore tiny vessels role in cardiovascular diseases
6. Help Minnesota Man Reach His Goal of Raising Money & Awareness Sponsor 1 of his “200 Perfect Jumps for Parkinson's Disease"
7. China facing public health crisis with projected increase in cardiovascular disease by 2030
8. UABs Whitley named distinguished physician by Pediatric Infectious Diseases Society
9. Fear of pandemic influenza clogs EDs even when disease is not present
10. Aspirin May Increase Risk of Crohns Disease
11. Phase II study of an oral therapy for Gaucher disease yields positive results
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Rare disease in Amish children sheds light on common neurological disorders
(Date:5/26/2016)... ... , ... Development Team of Pixel Film Studios Announced The Release of TranSweep, ... transition tool will keep a consistent flow to your project while adding interesting visuals ... TranSweep is an all new layered style transition tool for Final Cut Pro ...
(Date:5/26/2016)... , ... May 26, 2016 , ... In Madeira Beach ... mainland by a single drawbridge, citizens formed an organization, Madeira Beach United, to oppose ... and change the small town center to a high rise urban environment. , According ...
(Date:5/26/2016)... ... 2016 , ... According to the Webster’s dictionary, a hippie is defined as ... one company is going against the norm with a line of all-natural skincare that’s ... the green space is proud to announce its latest retail partnership with the Vitamin ...
(Date:5/26/2016)... California (PRWEB) , ... May 26, 2016 , ... ... Barbara this Memorial Day weekend to host their second pop-up shop for three ... Diego fashion forward brand to the Santa Barbara community, a community full of ...
(Date:5/26/2016)... Malvern, PA (PRWEB) , ... May 26, 2016 ... ... Sharon Wolf has been hired as FluidEdge’s Vice President of Business Intelligence and ... health analytics, Wolf has demonstrated success leading teams as a healthcare business and ...
Breaking Medicine News(10 mins):
(Date:5/25/2016)... May 25, 2016 Digital Health Dialog, ... it by the US Patent and Trademark Office ... includes proprietary processes for electronic opt-­in and processing ... wellness programs, HIPAA compliance and otherwise. ... "Our technology allows for individuals ...
(Date:5/24/2016)... , May 24, 2016 ... den Markt gebracht, die es Ärzten erlaubt, ihre ... zu behandeln: MDLinking kombiniert Live Streaming mit einer ... Umfeld zu kommunizieren. Mediziner in Europa, Afrika, Asien ... sich bereits für die Plattform registriert. ...
(Date:5/24/2016)... , May 24, 2016  Diana Russell suffers ... her organs from the inside out.  This disease has ... dependent on her children and grandchildren to leave her ... wheelchair, Diana,s family cannot haul the wheelchair.  So if ... the car, and Diana is left to wait for ...
Breaking Medicine Technology: