Navigation Links
Gene discovery may shed light on kidney disease

In a finding that may have broader implications for understanding kidney disorders, genetics researchers at The Children's Hospital of Philadelphia have identified a second gene that gives rise to Alagille syndrome, a genetic developmental disease that affects multiple organs. The Children's Hospital team previously discovered the first gene associated with this disease.

The researchers found that mutations in the NOTCH2 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 ducts found in the livers of man y 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:Children's Hospital of Philadelphia


Related biology news :

1. Protein discovery could unlock the secret to better TB treatment
2. Purdue proves concept of using nano-materials for drug discovery
3. UCSD discovery may help extend life of natural pesticide
4. Leprosy microbes lead scientists to immune discovery
5. Biochemists report discovery of structure of major piece of telomerase; implications for cancer
6. Researchers make surprise discovery that some neurons can transmit three signals at once
7. Important discovery about second most fatal cancer
8. Harmless virus may hold key to more effective HIV drug discovery
9. Fundamental discovery -- Bone fracture
10. Genetic discovery could lead to drought-resistant plants
11. Gene discovery sheds light on causes of rare disease, cancer
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/28/2016)... First quarter 2016:   , Revenues amounted ... quarter of 2015 The gross margin was 49% (27) ... the operating margin was 40% (-13) Earnings per share ... operations was SEK 249.9 M (21.2) , Outlook   ... M. The operating margin for 2016 is estimated to ...
(Date:4/15/2016)... Research and Markets has announced ... 2016-2020,"  report to their offering.  , ... global gait biometrics market is expected to grow ... 2016-2020. Gait analysis generates multiple variables ... to compute factors that are not or cannot ...
(Date:3/29/2016)... LegacyXChange, Inc. (OTC: LEGX ... Protect are pleased to announce our successful effort to ... of writing instruments, ensuring athletes signatures against counterfeiting and ... athletes on LegacyXChange will be assured of ongoing proof ... Bill Bollander , CEO states, "By inserting ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... Hematology Review, 2016;12(1):22-8 http://doi.org/10.17925/OHR.2016.12.01.22 ... , the peer-reviewed journal from touchONCOLOGY, Andrew ... escalating cost of cancer care is placing an ... result of expensive biologic therapies. With the patents ...
(Date:6/23/2016)... ... June 23, 2016 , ... ClinCapture, the only free validated ... will showcase its product’s latest features from June 26 to June 30, 2016 ... on Disrupting Clinical Trials in The Cloud during the conference. DIA (Drug ...
(Date:6/23/2016)... ... June 23, 2016 , ... Velocity ... intelligent tools designed, tuned and optimized exclusively for Okuma CNC machining centers at ... result of a collaboration among several companies with expertise in toolholding, cutting tools, ...
(Date:6/23/2016)... June 23, 2016 ReportsnReports.com ... report to its pharmaceuticals section with historic and ... and much more. Complete report on ... pages, profiling 15 companies and supported with 261 ... http://www.reportsnreports.com/reports/601420-global-cell-culture-media-industry-2016-market-research-report.html . The Global Cell ...
Breaking Biology Technology: