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:11/28/2016)... 2016 "The biometric system ... The biometric system market is in the growth ... near future. The biometric system market is expected to ... a CAGR of 16.79% between 2016 and 2022. Government ... technology in smartphones, rising use of biometric technology in ...
(Date:11/22/2016)... , Nov. 22, 2016   MedNet Solutions , ... entire spectrum of clinical research, is pleased to announce ... LiveWire Healthcare and Life Sciences Awards as "Most ... off an unprecedented year of recognition and growth for ... over 15 years. iMedNet ™ ...
(Date:11/17/2016)... LONDON , Nov. 17, 2016 Global Market ... and Public Biobanks (Disease-Based Banks, Population-Based Banks and Academics) market ... Geographical analysis for Private Biobanks shows the highest Compounded Annual ... Asia-Pacific region during the analysis period 2014-2020. ... a CAGR of 9.95% followed by Europe ...
Breaking Biology News(10 mins):
(Date:12/7/2016)... AUSTIN, Texas , Dec. 7, 2016 /PRNewswire/ ... development of revolutionary immunogene therapy treatments, today announced ... healthcare practice within a leading strategic communications and ... strategic communications program. The program will combine investor ... the objective of raising the profile of Genprex ...
(Date:12/7/2016)... ... December 07, 2016 , ... ... recovery solutions for industrial facilities, today announced that one of the nation’s fastest ... use Cambrian’s novel water-energy purchase agreement (WEPA). Under the WEPA, a first for ...
(Date:12/7/2016)... Massachusetts (PRWEB) , ... December 07, 2016 , ... Kara Dwyer Dodge grew up hearing ... Dwyer, a third-generation fisherman in Scituate, Mass., found a sea turtle entangled in the lines ... where the turtle became a minor sensation because no one could remember ever seeing one ...
(Date:12/6/2016)... (PRWEB) , ... December 06, 2016 , ... ... on December 1, 2016 asking the Federal Drug Administration (FDA) to consider OA ... of OA, OARSI is concerned about the growing population of OA patients, many ...
Breaking Biology Technology: