Navigation Links
Study uncovers mutation responsible for Noonan Syndrome

Scientists have discovered that mutations in a gene known as SOS1 account for many cases of Noonan syndrome (NS), a common childhood genetic disorder which occurs in one in 1,000-2,500 live births. NS is characterized by short stature, facial abnormalities, and learning disabilities, as well as heart problems and predisposition to leukemia.

Led by researchers at Harvard Medical School-Partners Healthcare Center for Genetics and Genomics (HPCGG) and Beth Israel Deaconess Medical Center (BIDMC), the findings are reported in the December issue of Nature Genetics, which appears on-line today.

"Noonan syndrome is the most common single gene cause of congenital heart disease," explains co-senior author Benjamin Neel, MD, PhD, Director of the Division of Cancer Biology at BIDMC and professor of medicine at Harvard Medical School (HMS).

"Although previous work had identified mutations in the PTPN11 gene as the cause of Noonan syndrome in nearly 50 percent of cases [and mutations in an oncogene known as KRAS in a small subset of severe cases] the identity of the gene or genes responsible for fully half the cases had not been elucidated," Neel said.

To identify candidate genes, a group led by HMS instructor Amy Roberts, MD, and director of HPCGG Raju Kucherlapati, PhD, conducted genetic analysis of over 100 children with Noonan syndrome. This large cohort of NS patients had neither PTPN11 nor KRAS mutations.

"From this group, we identified SOS1 mutations in approximately 20 percent of the cases," explains Kucherlapati, the Paul C. Cabot professor of genetics at HMS. After modeling the positions of the mutations on crystal structures of SOS1, the scientists made recombinant versions of the mutants and expressed them in mammalian cells, where it was discovered that they promoted excessive activation of RAS and its downstream target, MAP kinase, the same pathway activated by PTPN11 mutations.

"These results are the fi rst example of activating mutations in an exchange factor in human disease," notes Neel, explaining that for families at risk for Noonan syndrome, the findings will aid in prenatal diagnosis and genetic counseling for the disorder.

"Furthermore," Neel adds, "because the other two genes that cause Noonan syndrome are also mutated in several types of leukemia and solid tumors, our findings may also expand our knowledge of cancer pathways."
'"/>

Source:Beth Israel Deaconess Medical Center


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/1/2016)... , Feb. 1, 2016  Today, the first ... (AHA) announced plans to develop a first of its ... power of IBM Watson. In the first application of ... IBM (NYSE: IBM ), and Welltok will create ... health assessments with cognitive analytics, delivered on Welltok,s health ...
(Date:1/25/2016)... 25, 2016  Glencoe Software, the world-leading supplier of ... industries, will provide the data management solution OMERO Plus ... Photo - ... Phenotypic analysis measures the characteristics and ... comparisons between states such as health and disease, the ...
(Date:1/20/2016)... 20, 2016   MedNet Solutions , an innovative ... of clinical research, is pleased to announce the attainment ... are the result of the company,s laser focus on ... , it,s comprehensive, easy-to-use and highly affordable cloud-based ... Key MedNet growth achievements in 2015 include: ...
Breaking Biology News(10 mins):
(Date:2/11/2016)...   BioInformant announces the February 2016 release ... Opportunities, Tools, and Technologies – Market Size, Segments, Trends, ... The first and only market ... BioInformant has more than a decade of historical information ... stem cell type. This powerful 175 page global strategic ...
(Date:2/11/2016)... ... February 11, 2016 , ... ... cell treatment clinic in Quito, Ecuador. The new facility will provide advanced protocols ... patients from around the world. , The new GSCG clinic is headed ...
(Date:2/10/2016)... Feb. 10, 2016  The Maryland House of Delegates ... announced that University of Maryland School of Medicine Dean ... University of Maryland Medical System President and CEO ... Medallion," the highest honor given to the public by ... Dean Reece and Mr. Chrencik for their ...
(Date:2/10/2016)... New York, and New York, New York (PRWEB) , ... ... ... Regeneron Pharmaceuticals Inc. (NASDAQ: REGN) today announced that it ... and develop new vaccines and immunotherapies for infectious diseases and cancer. ...
Breaking Biology Technology: