Dowling-Degos disease is a hereditary pigmentation disorder that generally progresses harmlessly. However, some of those affected also develop severe skin inflammation. An international team of researchers under the leadership of the University of Bonn has now found a cause for this link. Their knowledge comes thanks to an animal that is known among aquarium owners for its characteristic pigmentation: the zebrafish. The results have now been published in the Journal of Clinical Investigation.
People with Dowling-Degos disease have a noticeably large number of dark pigment spots. These are frequently found in certain areas of the body, such as the face, neck, torso, hands, and the bending folds of the arms and legs. The pigmentation disorder generally progresses harmlessly; however, it can have a negative aesthetic effect.
Occasionally, those affected also develop extremely unpleasant skin inflammation, called acne inversa. This is not only painful but is also associated with festering blisters that can leave scars when they burst. The colonization of microorganisms on the affected areas of skin also creates unpleasant body odor. Acne inversa has a chronic progression; a permanent solution is only provided by surgery.
“We have genetically examined 90 people with Dowling-Degos disease since 2005,” explains Prof. Regina Betz from the Institute of Human Genetics at the University Hospital of Bonn. “Six of them also suffered from acne inversa.” The scientists found a special characteristic in this subgroup: the patients displayed mutations in what is known as the PSENEN gene.
It has been known that PSENEN mutations can cause acne inversa. “However, we were able to show for the first time that changes in this gene primarily cause Dowling-Degos disease and around half of the mutation carriers develop acne inversa,” emphasizes Damian Ralser, who is currently working on his doctorate at the Institute of Human Genetics.
To do this, the scientists used an animal that should be known to many aquarium enthusiasts due to its striking pigmentation: the zebrafish. However, the characteristic blueish black stripes, which give the fish its name, only form over time. The eyelash-sized zebrafish larvae are more or less transparent.
Fish as a model organism
Many processes in the body can thus be observed easily under an optical microscope. For this reason, the zebrafish is now used as a model organism by scientists around the globe. At the University of Bonn, Prof. Benjamin Odermatt from the Anatomical Institute is researching how zebrafish repair defective nerve tissue.
Zebrafish also have the PSENEN gene. “In order to be able to research more closely what effect PSENEN has, we, in collaboration with Prof. Odermatt, deactivated the gene in some zebrafish larvae and then compared these with normal larvae under the microscope,” explains Damian Ralser.
The pigment cells – the melanocytes – usually wander in a certain direction in the zebrafish larvae. This ensures that the characteristic striped pattern develops over time. However, the pigment cells wandered back and forth aimlessly in animals in which the functioning of PSENEN was disrupted. They ultimately collected in unusual places to form clearly visible patches – similar to people with Dowling-Degos disease.
Only a small proportion of all Dowling-Degos patients carry a PSENEN mutation. “There are also other disease genes that lead to the pigmentation disorder,” says Betz. She recommend that all those affected undergo testing. If a disrupted PSENEN gene is the actual cause, there is a significantly increased risk of also suffering from acne inversa. However, the scientist emphasizes that no one is exposed to this risk without protection: “This severe form of acne develops in particular in PSENEN mutation carriers who smoke a lot or who are overweight.”
Publication: Damian Ralser et al.: Mutations in gamma-secretase subunit–encoding PSENEN underlie Dowling-Degos disease associated with acne inversa; Journal of Clinical Investigation; DOI: 10.1172/JCI90667
Prof. Regina Betz
Institute of Human Genetics
University of Bonn
Tel. +49 (0)228/28751023
Prof. Benjamin Odermatt
University of Bonn
Tel. +49 (0)228/739021
Johannes Seiler | idw - Informationsdienst Wissenschaft
How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine
Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy