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."


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:

(Date:11/28/2015)... ... 28, 2015 , ... StatRad , a leading provider ... and Claude Hooton to its board of directors. The announcement comes as the ... Annual Meeting and continues to strategically transform its focus from being a teleradiology ...
(Date:11/27/2015)... (PRWEB) , ... November 28, 2015 , ... There is ... we outperform our billings from last year? , This question has not been an ... are coming to the retirement age and the younger workforce don’t share the same ...
(Date:11/27/2015)... ... ... A team of Swiss doctors has released a report on mesothelioma relapse ... the findings on the website. Click here to read the details now. ... who were treated with chemotherapy followed by EPP surgery. Among the 106 patients who ...
(Date:11/27/2015)... ... 2015 , ... ProSidebar: Fashion is a set of 30 kinetic ... Fasion, video editors can easily add an informative sidebar to any FCPX production. ... presets featuring self-animating drop zones, lines, bars, and text with the ease of FCPX's ...
(Date:11/27/2015)... ... November 27, 2015 , ... The moment ... itself for not only fulfilling the needs of advisers and clients but going ... price and providing top-tier customer service. However, there's always room for improvement, which ...
Breaking Medicine News(10 mins):
(Date:11/29/2015)... 2015 CIVCO Medical Solutions will demonstrate ... Radiological Society of North America ... November 29 – December 4, 2015. The ... customers unrivaled versatility, enhanced user experience and deliver ... --> --> ...
(Date:11/27/2015)... Niederlande, November 27, 2015 ... bei fortgeschrittenem Krebs.   --> Ein ... fortgeschrittenem Krebs.   --> Ein ... fortgeschrittenem Krebs.   Clinical Cancer Research ... Clinical Cancer Research vom 6. November ...
(Date:11/26/2015)... India , November 27, ... --> --> ... personal emergency response system (PERS) ... steadily for 5 years with ... region expected to see a ...
Breaking Medicine Technology: