Navigation Links
Rare developmental disorder linked to tumor-suppressing protein, Stanford researchers find
Date:8/3/2014

CHARGE, which affects 1 in 10,000 babies, is an acronym whose letters stand for some of the more common symptoms of the condition: coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness.

Originally, the researchers were examining the tumor-suppressive properties of the protein, called p53, not investigating developmental disorders. But when a mouse model developed a strange set of deficiencies, the researchers followed a trail of clues that led them to link p53 with CHARGE syndrome.

"It was a very big surprise and very intriguing," said Jeanine Van Nostrand, PhD, lead author of a paper describing the research and a former Stanford graduate student, now at The Salk Institute for Biological Studies. "P53 had never before been shown to have a role in CHARGE."

The paper will be published online Aug. 3 in Nature. The senior author is Laura Attardi, PhD, professor of radiation oncology and of genetics.

Cellular quality control regulator

The researchers originally created a mouse model that expressed a mutated form of the protein, known as p53, to investigate the behavior of p53 in suppressing tumors. Mice expressing only the mutated protein survived. But to their surprise, heterozygous mice, or those with one copy of the mutated p53 and one normal copy, developed symptoms of CHARGE and died in utero.

P53 is a cellular quality-control regulator. When it spots an ailing cell, it triggers other proteins to kill the cell or arrest its division. In a developing human or mouse, other proteins switch off p53 so it doesn't inadvertently kill important cells. The mutated form of p53 created by the researchers had a disabled off-switch, but it also couldn't communicate with other proteins to spark the cellular death. Therefore, a mouse containing only the mutated p53 survived to adulthood.

But when mice had one copy of a mutated p53 gene and one normal copy, the resultant proteins formed hybrids. These hybrid p53 proteins couldn't be turned off, but they retained the ability to trigger cellular death. Interestingly, these proteins only affected certain types of cells, causing the symptoms of CHARGE. The results suggest that p53 may play a role in other developmental disorders, Attardi said.

"It really reiterates how carefully p53 must be regulated," Attardi said. "It needs to be turned on at the right time and place. If it's not, it can cause damage."

CHARGE linked to gene mutation

The mechanisms of CHARGE syndrome remain a mystery, although it has been linked to a mutation in a gene called CHD7. Attardi's team examined the connection between p53 and CHD7. They discovered that the CHD7 protein can keep p53 turned off.

By linking p53 with CHARGE, this study elucidates molecular pathways that could be used to develop CHARGE therapies, said co-author Donna Martin, MD, PhD, associate professor of pediatrics and of human genetics at the University of Michigan Medical School and an expert on CHARGE.


'/>"/>

Contact: Rosanne Spector
manishma@stanford.edu
650-725-5374
Stanford University Medical Center
Source:Eurekalert

Related medicine news :

1. DC Adventure Team Challenge Thrills Developmentally-Disabled Participants
2. Pop.Earth & Root Health Launch Colorado Yoga Program for Children with Autism Spectrum Disorder & Developmental Disabilities
3. Developmental psychologist explains her lifes work studying the mysteries of the mind
4. Zebrafish research meeting to highlight advances in genetics and developmental biology
5. RSNA: Brain Chemical Ratios Help Predict Developmental Delays in Preterm Infants
6. Brain chemical ratios help predict developmental delays in preterm infants
7. Congenital heart defects affects long-term developmental outcome
8. Researchers call for health-care changes to help adults with developmental disabilities
9. New study on neurodevelopmental effects of prenatal exposure to paracetamol
10. Focus on developmental approach to obesity in children and adolescents
11. Let's Help Children Read - A New Vision of Reading Readiness Through Developmental Movement from Katie Johnson, Author of Red Flags for Primary Teachers
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/17/2019)... (PRWEB) , ... September 17, 2019 , ... Lubin ... reception fundraiser. Gather for GRIN2B will be held at Found Kitchen and ... , Proceeds will help fund research on GRIN2B-Related Neurodevelopmental Disorder, a rare condition that ...
(Date:9/17/2019)... ... September 17, 2019 , ... ... Warriors , with the goal of providing resources to assist researchers and encourage ... a progressive disease causing abnormal iron deposits in the brain. , BPAN ...
(Date:9/17/2019)... ... September 17, 2019 , ... ... Experience" Open House day on Pacifica's Lambert Campus, 249 Lambert Road, Carpinteria, ... Psychology, the Humanities, Clinical Psychology, Counseling Psychology, and Mythological Studies. Program Faculty ...
(Date:9/12/2019)... ... September 12, 2019 , ... Donaldson ... national scale in two recent and well-renowned listing publications, the Inc. 5000 and ... for the 2019 year. , Dr. Jeffrey Donaldson, CEO and owner of ...
(Date:9/11/2019)... ... September 11, 2019 , ... A September 2 article ... weight loss surgery were significantly less likely to suffer heart attacks, strokes, kidney failure, ... bariatric surgery. Los Angeles-based weight loss surgery specialists Dr. Feiz and Associates says the ...
Breaking Medicine News(10 mins):
(Date:9/17/2019)... ... September 17, 2019 , ... ... today the launch of RegistryConnect , the first and most compliant online ... RegistryConnect includes care-matching, schedule recording, client and caregiver relationship management. RegistryConnect is available ...
(Date:9/17/2019)... ... September 17, 2019 , ... ... on sexual health, reproductive justice, contraception and consent with student and faculty from ... sexual health experts which included Francisco Ramirez, MPH; Elise Schuster, MPH; Raffaele M. ...
(Date:9/17/2019)... LUIS OBISPO, Calif. (PRWEB) , ... September 17, 2019 , ... Summer is a time ... of it is good for our teeth and gums. Dr. Douglas Ng, family dentist ... , Warm weather is the time for ice cream, and popsicles and ice-filled cold drinks ...
Breaking Medicine Technology: