Ichthyosis vulgaris research update
~ Dermatology & Genetic Medicine, Dundee
Filaggrin gene discovery
The research group in Dundee, Scotland, led by Professor Irwin McLean first discovered the changes in the filaggrin gene that cause ichthyosis vulgaris in 2006. Since this time we have been working hard to learn more about the filaggrin gene and how it works within the skin.
We each have two copies of the filaggrin gene. Mutations or ‘spelling mistakes’ in filaggrin are surprisingly common: they are found in 1 in 10 people in the UK. Approximately 1 in 100 people in the UK population have a mutation in both copies and this results in dry, scaly skin – ichthyosis vulgaris. People with a mutation in just one of their copies of filaggrin may have mild dry skin or their skin may look normal, but they are more prone to develop the red, itchy skin characteristic of eczema. Not all eczema cases have filaggrin gene mutations, but eczema caused by filaggrin tends to start early in life (as a baby or toddler) and may persist throughout childhood and into adult life.
Filaggrin is important in protecting against allergy
Recent research has shown that changes in the filaggrin gene can also lead to other allergic diseases, including hay fever, asthma and peanut allergy. We think this happens because skin which has less filaggrin provides a more leaky barrier between the body and the outside world. Dust, pollen and food substances may therefore pass through the skin barrier and set up an allergic response in the skin, in the bloodstream or in the lungs, resulting in allergic disease.
Research around the world
Many other research groups around the world are also looking at the filaggrin gene. There are different mutations in different populations, so the spelling mistakes in filaggrin that we have found in our patients from the UK and Ireland are not often found in Africa or Asia. Researchers in China, Singapore & Japan have found many different filaggrin mutations in their local populations, but they all seem to have a similar effect on the skin, producing dry skin or ichthyosis vulgaris.
Hope for better treatments
The filaggrin gene is a long and complex code and it includes one piece of sequence which repeats itself many times. This is the code for a long protein that is chopped up within skin cells to produce many copies of filaggrin protein. The number of repeats in each of our filaggrin genes varies – some filaggrin genes have 10 repeats, some have 11 and some have 12 repeats.
Our most recent research has shown that people with fewer filaggrin repeats are more likely to develop eczema, whilst people with more filaggrin repeats have more filaggrin and are protected from eczema. This gives us hope that future treatments aimed at increasing filaggrin in the skin to treat ichthyosis vulgaris may also help to protect against eczema.
Irwin McLean and his team are working on strategies to increase the amount of filaggrin produced by skin cells. Early results using skin cells in the laboratory are encouraging, but it will take several years before these treatments are ready to be trialed in people. We will keep you informed!
Dr Sara Brown
Wellcome Trust Intermediate Clinical Fellow & Honorary Consultant Dermatologist,
University of Dundee
Professor Irwin McLean
Professor of Human Genetics,
University of Dundee