Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers discover novel gene and new pathomechanism for Joubert syndrome

29.06.2011
Joubert syndrome is a genetic condition that is characterized by a complex brain malformation.

An international team of researchers led by the human geneticist Dr. Hanno Bolz (Institute of Human Genetics, University Hospital of Cologne) and Dr. Bernhard Schermer (head of the Nephrolab Cologne) has identified defects in the KIF7 gene in patients with Joubert syndrome and uncovered a novel mechanism for this disease. The study has been published online in The Journal of Clinical Investigation and will appear in the July print issue.

The team investigated an Egyptian family that tested negative for all known Joubert genes. “Because the parents in this family were related, it was highly suited for identifying a novel gene for Joubert syndrome” says Bolz.

The geneticists localized the disorder to the long arm of chromosome 15 (designation for the new disease gene locus: JBTS12) and subsequently identified mutations in the KIF7 gene in the Egyptian family and in additional patients. KIF7 encodes a ciliary motor protein.

Cilia are antenna-like structures on the cell surface, and many research laboratories worldwide focus on elucidating the functions of this organelle. Cilia are sensory organelles that transmit environmental signals into the cell. An increasing number of genetic diseases have been linked to ciliary dysfunction (the so-called “ciliopathies”).

One patient was found to carry a KIF7 mutation together with two mutations in a known Joubert gene, TMEM67. “This is a phenomenon in ciliopathy genetics that we became more and more aware of over the recent years” explains Dr. Bolz. In 2010, the group has already described similar “oligogenic inheritance” for another ciliopathy, Usher syndrome, also in The Journal of Clinical Investigation. “Besides, KIF7 represents a prime candidate for mono- and oligogenic forms of related ciliopathies, namely Meckel-Gruber, Senior Loken, and Bardet-Biedl syndromes, Leber congenital amaurosis, and nephronophthisis” Bolz adds.

“Chemical substances such as hormones or cytokines bind to ciliary receptors which initiates different activities in the cell” says Dr. Bernhard Schermer. “In the kidney, the urine flow deflects the cilia. Through this, the cells receive informations on flow rate and direction.”

It recently became clear that KIF7 plays a role in Sonic hedgehog (Shh) signaling, a pathway that is crucial for embryonic development. Shh receptors localize exclusively to the cilium. “Our data indicate a function of KIF7 that goes beyond the cilium and hedgehog signaling, to basic cellular processes: Targeted inactivation of KIF7 leads to only mild impairment of cilia formation, but causes dramatic changes of other organelles. As a common basis for these pathologies, we have identified changes in the microtubular cytoskeleton.”

This cytoskeleton regulates important routes of transport through the cell and thereby influences the cell’s shape and orientation. “Our findings indicate a novel pathomechanism for Joubert syndrome that may also be the basis for other ciliopathies” Dr. Schermer concludes.

Besides the two teams from Cologne, researchers from the Ain Shams University in Cairo, the Department of Paediatric Neurology, University Children’s Hospital of Zurich, the Department of Pediatrics, Innsbruck Medical University, the German Cancer Research Center, Heidelberg, des DKFZ in Heidelberg, Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg, the Institute of Human Genetics, University Hospital of Schleswig-Holstein, the Department of Radiology and the Department of Anatomy, University of Cologne, contributed to the study.

The study was supported by the Deutsche Forschungsgemeinschaft, the Pro Retina Foundation Germany, Köln Fortune (University Hospital of Cologne), and the Gertrud Kusen-Stiftung.

Publication:
Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics.
Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenke GC, Fabretti F, Janecke AR, Ebermann I, Nürnberg G, Nürnberg P, Zentgraf H, Koerber F, Addicks K, Elsobky E, Benzing T, Schermer B, Bolz HJ.
The Journal of Clinical Investigation, 2011.
doi:10.1172/JCI43639
http://www.jci.org/articles/view/43639
Contact:
PD Dr. Hanno Jörn Bolz
Institute of Human Genetics, University Hospital of Cologne, Germany
(currently at the Bioscientia Center for Human Genetics, Ingelheim, Germany)
Phone: +49 6132 781-206
E-Mail: hanno.bolz@uk-koeln.de
PD Dr. Bernhard Schermer
Nephrologic Research Laboratory
Klinik IV für Innere Medizin
Uniklinik Köln
Telefon: 0221 478-89030
E-Mail: bernhard.schermer@uk-koeln.de
Christoph Wanko
Public Relations Officer
Uniklinik Köln
Telefon: 0221 478-5548
E-Mail: christoph.wanko@uk-koeln.de

Christoph Wanko | idw
Further information:
http://www.uk-koeln.de

More articles from Life Sciences:

nachricht UNH researchers create a more effective hydrogel for healing wounds
21.11.2018 | University of New Hampshire

nachricht Removing toxic mercury from contaminated water
21.11.2018 | Chalmers University of Technology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First diode for magnetic fields

Innsbruck quantum physicists have constructed a diode for magnetic fields and then tested it in the laboratory. The device, developed by the research groups led by the theorist Oriol Romero-Isart and the experimental physicist Gerhard Kirchmair, could open up a number of new applications.

Electric diodes are essential electronic components that conduct electricity in one direction but prevent conduction in the opposite one. They are found at the...

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Removing toxic mercury from contaminated water

21.11.2018 | Life Sciences

New China and US studies back use of pulse oximeters for assessing blood pressure

21.11.2018 | Medical Engineering

Exoplanet stepping stones

21.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>