Navigation Links
Mutations impair childhood growth and development by disrupting organization of chromosome pairs
Date:5/29/2012

Researchers studying rare genetic disorders have uncovered insights into those diseases in biological structures that regulate chromosomes when cells divide. Focusing on the cohesin complex, a group of proteins forming a bracelet that encircles chromosome pairs, scientists have discovered mutations that disrupt cohesin, causing a recently recognized class of diseases called cohesinopathies.

"We are learning more about how these genetic abnormalities that affect cohesin play a role in human development," said study leader Matthew A. Deardorff, M.D., Ph.D., a specialist in pediatric genetics at The Children's Hospital of Philadelphia's Center for Cornelia deLange Syndrome and Related Diagnoses.

The research, carried out in children, cell cultures, and zebrafish, appeared May 24 in the American Journal of Human Genetics. Deardorff's co-study leader was Frank J. Kaiser, Ph.D., of the University of Lubeck in Germany.

The cohesin complex is already known to be involved in Cornelia deLange syndrome (CdLS), a multisystem genetic disease affecting an estimated 1 in 10,000 children. The disease has a range of severity, but classically includes mental retardation, impaired growth, heart defects, feeding problems, deformed arms and hands, and distinctive facial features.

Researchers at The Children's Hospital of Philadelphia previously were the first to discover gene mutations that cause CdLS, including forms of the disease with mental retardation and often severe limb abnormalities. The current study identified another gene, RAD21, that when mutated, causes very mild cognitive and physical impairments.

The study team first performed a genome-wide analysis of 101 children with typical CdLS and 189 children having overlapping features of the disease. None of the children had mutations in the three genes already known to cause CdLS. They identified a six-year-old boy with a deletion in a section of chromosome 8 that contains the RAD21 gene, which was known to express a cohesin protein but not previously known to cause disease. As an infant, the boy had been diagnosed with facial features similar to those of CdLS, and subsequently experienced growth retardation, but had normal cognitive development.

The researchers then focused on three additional children with deletions in RAD21 and two children with mutations within the gene, and found a similar patternphysical features, such as short stature and distinctive facial features, overlapping with some of those seen in cohesin disorders, but with only minor cognitive delays. "These findings suggest that children who are very mildly affected may go undiagnosed," said Deardorff.

The research team did further studies in cell cultures and a zebrafish model to investigate molecular mechanisms involved in cohesin disorders. The cohesin complex includes four proteins that join in a bracelet-like structure that surrounds sister chromatids, the identical pairs that result from chromosome duplication prior to cell division. RAD21, the protein expressed by the gene with the same name, forms a clasp that closes the bracelet. A mutated RAD21 gene weakens that clasp, impairing cohesion's normal abilities to repair damage to DNA.

However, Deardorff added, the lab research does not currently explain the full sequence of molecular events, and further studies will investigate knowledge gaps in the process.

As the cost of whole-genome sequencing is rapidly dropping, Deardorff expects researchers to discover additional genes involved in cohesinopathies, offering further clues to how these diseases function in human development. "For now we can expect that patients with the RAD21 mutation will be less severely affected than those with classical CdLS," he said. "As we better understand the mechanisms of these congenital diseases, we'll continue to seek opportunities to devise more effective treatments."


'/>"/>

Contact: John Ascenzi
ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert  

Related medicine news :

1. Cancer may require simpler genetic mutations than previously thought
2. Scientists make breakthrough in bile duct cancer with discovery of new gene mutations
3. Researchers Find Gene Mutations That May Be a Key to Autism
4. Stealth properties of cancer-causing genetic mutations identified
5. Cancer sequencing initiative discovers mutations tied to aggressive childhood brain tumors
6. Mutations in 2 Genes Linked to Rare Autism-Related Disorder
7. Gene Mutations May Boost Ovarian Cancer Survival: Study
8. Gene Mutations Linked to Thyroid Cancer Risk: Study
9. Massive DNA search uncovers new mutations driving blood cancer
10. Panel of melanoma mutations opens door to new treatment possibilities
11. Linking of mutations in 12 genes to ovarian cancer may lead to more effective prevention
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Mutations impair childhood growth and development by disrupting organization of chromosome pairs
(Date:2/17/2017)... ... February 17, 2017 , ... Program will ... Trinity Health and the U.S. Soccer Foundation announced today that they have awarded ... Soccer for Success, the Foundation’s soccer mentoring program, teaches kids the fundamentals of ...
(Date:2/17/2017)... ... February 17, 2017 , ... PrideStaff, a national staffing ... named to Staffing Industry Analysts' 2017 "Staffing 100 North America" list. , ... notable contributions to the staffing industry over the last twelve months. Industry insiders ...
(Date:2/17/2017)... CO (PRWEB) , ... February 17, 2017 , ... Top ... annual International Healing NET Foundation Summit from February 21 - 23 in Beaver Creek, ... Foundation (HNF). This marks the Summit’s second year in Beaver Creek, hosting over 60 ...
(Date:2/16/2017)... York, New York (PRWEB) , ... February 17, ... ... work and determination. After what took over 10 years of research, development and ... technology, NTX Technology™. NTX Technology™ is a patented compound of FDA approved ingredients ...
(Date:2/16/2017)... ... February 17, 2017 , ... The Price Agency, a ... and entrepreneurs in the Birmingham area, is announcing an ongoing charity event to ... her medically challenged son, Anius. , Anius is medically complex with diagnoses consisting ...
Breaking Medicine News(10 mins):
(Date:2/16/2017)... -- Newly published research from the CVS Health (NYSE: ... private retailer can play in restricting access to tobacco ... in the American Journal of Public Health , ... all CVS Pharmacy stores reduced the number of cigarette ... impact on those who bought cigarettes exclusively at CVS ...
(Date:2/16/2017)... , Feb. 16, 2017  AcelRx Pharmaceuticals, Inc. ... company focused on the development and commercialization of ... pain, announced that Vincent J. Angotti ... member of the company,s board of directors, effective ... two decades of experience leading executive and commercial ...
(Date:2/16/2017)... , Feb. 16, 2017  Prescription pain medications provided ... visit are necessary for long-term opioid use to take ... 16 th edition of The New England ... physicians see more patients in acute pain than in ... , MD, FACEP, president of the American College of ...
Breaking Medicine Technology: