Navigation Links
Second Alagille Syndrome Gene discovered: More information on kidney disease

Genetics researchers at the Children's Hospital of Philadelphia have discovered a second gene that causes Alagille syndrome, a developmental disease with a genetic basis that affects many organs.//

This finding may have broader implications in the understanding of kidney disorders. The Children's Hospital team had earlier discovered the first gene associated with this syndrome.

The researchers found that mutations in the NOTCH 2 gene were linked to kidney abnormalities in patients and families. "While Alagille syndrome is relatively rare, organ diseases are not rare, and our findings suggest that genes on this biological pathway may have a broader role in kidney disorders," said study leader Nancy B. Spinner, Ph.D., a geneticist at The Children's Hospital of Philadelphia.

The study appears in the July issue of the American Journal of Human Genetics.

Dr. Spinner led the Children's Hospital team that identified mutations in the JAG1 gene as a cause of Alagille syndrome in 1997. Like the NOTCH2 gene analyzed in the current study, JAG1 is part of a signaling pathway that governs important processes in early human development.

Alagille syndrome, estimated to occur in one in 20,000 individuals, is a complex disorder, primarily affecting the liver, heart, eyes, face and skeleton. Some patients with Alagille syndrome have very mild symptoms or isolated problems, while others may have severe, life-threatening heart or liver defects.

Both the JAG1 and the NOTCH2 genes participate in the Notch signaling pathway. JAG1 codes for the ligand Jagged1, a signaling protein that triggers receptors in the pathway. The NOTCH2 gene codes for Notch2, which is one of those receptors. The pathway as a whole is active during embryonic development, and transmits signals to cells to develop into specialized organs. Mutations in those genes are thought to disrupt normal development, by, for instance, causing the defective bile du cts found in the livers of many patients with Alagille syndrome.

"Ligands and receptors are like keys and locks," said Dr. Spinner. "If either one is defective, it may interfere with normal growth and development."

Dr. Spinner's team previously determined that 94 percent of patients diagnosed with Alagille syndrome had mutations in the JAG1 gene. In the current study, they analyzed 11 patients with Alagille syndrome who did not have the JAG1 mutation, and found that two of them had mutations in NOTCH2. Furthermore, the patients had three family members, all mildly affected, who also had the same mutation. All five individuals had kidney disease.

Because their study identified only two families with NOTCH2 mutations, said Dr. Spinner, it is not definitive in establishing that those mutations cause a distinct variety of Alagille syndrome. However, it is the first study to report that mutations in the NOTCH2 gene cause human disease. Dr. Spinner is planning further studies to better characterize the role of NOTCH2 mutations and the Notch signaling pathway in the wider population of patients with kidney disorders.

She also will investigate liver involvement in Alagille syndrome under the Rare Diseases Clinical Research Network, recently established by the National Institutes of Health. "Part of the rationale for this research network is that, collectively, relatively rare diseases added together constitute a significant portion of the population," said David A. Piccoli, M.D., chief of Gastroenterology and Nutrition at Children's Hospital and a co-author of the study. "Another rationale is that studying relatively rare diseases may offer insights into more common diseases and into health in general."

SOURCE:EUREKALERT
'"/>




Related medicine news :

1. Second hope for men with erectile dysfunction
2. Second SARS suspect fuels worry in India
3. The Harmful Effects Of Secondhand Smoke
4. Second Hand Exposure To Smoke In Childhood Can Cause Respiratory Problems Later
5. HIV Virus Emerging Drug Resistant In UK, Prompting Fear Of A Second Epidemic
6. Women With Breast Cancer At Risk For Developing Second Cancer
7. Stroke Destroys Nearly 32, 000 Neurons In Just A Second!
8. Websites Are Judged In Less Than A Second
9. Can Second Hand Smoke Cause Cancer?
10. Second Hand Smoke Does No Harm
11. Healthy Kidney Removed From Patient, Second Surgery Needed
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:7/21/2017)... ... 21, 2017 , ... The Margarian Law Firm has filed a class ... ale for allegedly containing no ginger. Dr. Pepper produces the “Canada Dry” brand of ... Margaryan alleges Canada Dry Ginger Ale claims on its bottle that it is made ...
(Date:7/21/2017)... ... July 21, 2017 , ... “Kids aren't born knowing how to ... shoes,” says Suzanne Tucker, Founder of St. Louis-based positive education company Generation Mindful. To ... Kickstarter on Monday, July 21st. , The kit uses colorful, engaging and educational ...
(Date:7/21/2017)... CANADA (PRWEB) , ... July 21, 2017 , ... ... torn anterior cruciate ligament (ACL) offer patients improved quality of life five years ... for Sports Medicine’s Annual Meeting in Toronto, Ontario, Canada. The study followed ...
(Date:7/20/2017)... Boston, MA (PRWEB) , ... July 20, 2017 ... ... aggressive form of blood and bone marrow cancer that progresses rapidly without treatment. ... often recommended to reduce the chance of reoccurrence and relapse. With such ...
(Date:7/20/2017)... ... July 20, 2017 , ... ... in which their iMedSecure™ comes included with each system installation. RMT’s iMedHD2™ ... to remote participants for real-time collaboration and immediate decision-making requirements. While never ...
Breaking Medicine News(10 mins):
(Date:7/13/2017)... 2017  New York City-based market research firm Kalorama Information ... aware of.  From new products to new costs, to the ... recently completed study, Potential Pipeline Disruptors . ... 1.  Age-Driven Growth - True Impact Moment Arriving ... the impact the growing population and, to a more extreme ...
(Date:7/11/2017)... ROCKVILLE, Md. , July 11, 2017  The ... had estimated revenues of approximately $394.1 million in 2016.  ... a trend of solid growth, in particular as a ... oncology clinical practice, and the recent introduction of a ... the need for less-invasive testing of tumor biomarkers to ...
(Date:7/10/2017)... GAITHERSBURG, Md. , July 10, 2017 ... in non-animal test methods, is the recipient of a ... by the PETA International Science Consortium. The device, which ... be used to expose human lung cells to airborne ... lung. IIVS will use the VITROCELL® system for testing ...
Breaking Medicine Technology: