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:8/18/2017)... ... August 18, 2017 , ... Radabaugh & Associates, a ... communities in North-Central West Virginia, is embarking on a cooperative charity effort with ... area. , The Chestnut Mountain Ranch (CMR) is a Christ-centered boarding school for ...
(Date:8/18/2017)... ... 2017 , ... The Brian Gifford Agency, an Indiana-based firm providing asset protection ... Campagna Academy in a charity drive to provide for at-risk children and teens in ... Academy is a nonprofit organization that has offered critical programs to at-risk and foster ...
(Date:8/18/2017)... ... 2017 , ... “Emotions are sacred, valid, honored, encouraged. This is the memo ... Generation Mindful. To help change the mindset of parents and educators from punitive to ... the Time-In Toolkit, which launched on Kickstarter 3 weeks ago and fully funded in ...
(Date:8/18/2017)... ... 18, 2017 , ... Alcovit, a lime-flavored beverage that rids the body of ... its product now available through Jet.com. , After 25 years of development, the ... is designed to quickly detox the body thereby avoiding alcohol-induced hangovers. Whether you’re having ...
(Date:8/18/2017)... ... ... “Our Mountains to Climb: A Journey of Love and Faith Through Trials”: ... faith they shared to overcome struggles in life. “Our Mountains to Climb: A Journey ... Corcoran, a retired teacher and happily married since 1999; the author’s personal experiences drive ...
Breaking Medicine News(10 mins):
(Date:8/17/2017)... , August 17, 2017 DarioHealth ... Company with mobile health and big data solutions, ... agreements with domestic and non-U.S. investors for the ... and shares of the Company,s newly designated Series ... offerings. The Company expects to conduct a closing ...
(Date:8/15/2017)... HOUSTON , Aug. 15, 2017   Mostyn Law ... in Houston, Texas . The Mostyn Law ... the past 2 years. That is why Mostyn Law ... Texas to show its appreciation. Blood supplies ... to fall 5% short of hospital needs in August. That is ...
(Date:8/15/2017)... Aug. 15, 2017  Axium Pharmaceuticals Inc., the creator of the drug ... in the beginning stages of an IPO. The ... with the average cost of a prescription epilepsy drug being $450.00-$1200.00 for ... AXIUM PHARMACEUTICALS, INC ... Another staggering figure is the fact that Americans spent ...
Breaking Medicine Technology: