How a Defective Gene Causes Itchy Skin | Action Medical Research | Children's Charity

How a defective gene causes itchy skin

This research was completed on 6 January 2010

Published on 31 January 2008

Itchy skin is a common and distressing problem, yet the biological processes that cause it are little understood. Researchers working on this project have recently made a major breakthrough: they have discovered a defective gene that causes itching in a severe, inherited skin disorder. They are investigating whether the defects are linked to more common forms of itching, work that could eventually lead to new treatments.

What's the problem and who does it affect?

Little relief from maddening itching

We all know how annoying itchy skin can be. One little insect bite can be enough to drive someone to distraction. But some disorders cause severe and unremitting itching, an overwhelming desire to keep scratching and extensive damage to the skin. A disorder known as primary localised cutaneous amyloidosis (PLCA), which is being studied in this project, affects several thousand people in the UK, hundreds of thousands worldwide (1) There is no cure, and treatment provides only limited relief from the itching, which badly affects sufferers’ quality of life. Many feel the need to cover up their skin, which becomes thickened, discoloured and flaky. While itching is one of the most common problems to affect the skin, it is also something of a medical mystery. Little is known about the biological processes that take place in the skin to make us feel itchy. This hinders research into new treatments.

What is the project trying to achieve?

Breakthrough discovery of a defective gene

The researchers working on this project have already made an exciting discovery. They have identified genetic defects that cause the never-ending itching suffered by people with an inherited form of PLCA.(1) The defects are in a gene called the oncostatin M receptor-beta gene (OSMR). They were identified by studying a large family from Brazil, and then families from the UK and South Africa. The researchers have revealed that skin cells with the defective gene fail to respond properly to important signalling molecules, known as cytokines. Cytokines regulate inflammatory responses in skin cells. The defective cells’ failure to respond properly to the cytokines’ signals directly leads to itching. The researchers are building on their important discoveries to find out whether abnormalities in this signalling pathway cause itching in other cases of PLCA, which aren’t inherited, and in more common skin disorders, including lichen simplex and lichen planus.

What are the researchers' credentials?

Project LeaderProfessor J McGrath MD FRCP
Project team
  • Dr Andrew South BSc PhD
LocationSt John's Institute of Dermatology, Guy's Hospital, Division of Genetics and Molecular Medicine, King's College London in conjunction with the Division of Surgery and Molecular Oncology, Diagnostic/Treatment Centre for Genetic Skin Disease, University of Dundee
Other locations
  • Division of Surgery and Molecular Oncology, Diagnostic/Treatment Centre for Genetic Skin Disease, University of Dundee
DurationTwo years
Grant awarded31 October 2007
Start date1 December 2007
End date6 January 2010
Grant amount£118,394.00
Grant codeSP4269

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The Project Leader, Professor John McGrath, is a world expert in inherited skin diseases and the genetics that underlies them. He has published over 200 scientific papers on genetic skin diseases, including the discovery of several novel genes that are linked to skin disease. He is the current President of the European Society for Dermatological Research, co-ordinating research into skin disease across Europe. Unparalleled access to people with genetic skin disease means the project team is well placed to succeed. Indeed, the clinics that are visited by patients have close links with the project team’s state-of-the-art research laboratories at Guy’s Hospital, which were opened in April 2007.

Who stands to benefit from this research and how?

Helping in the search for new treatments

The researchers’ breakthrough discovery of the defective gene that causes itchy skin in PLCA is highly significant. It is the first ever discovery of a human gene abnormality that directly causes itching. It has already provided a unique insight into the chemicals and signals in the skin that cause itching. Researchers hope their on-going work will reveal even more. Itching has long been one of the least understood problems to affect the skin, even though it is one of the most common, and the most infuriating. Many different things can cause it, including insect bites, eczema, psoriasis, allergies, jaundice and leukaemia. An increased understanding of the biological processes that lead to itching provides a basis for developing new treatments, which are desperately needed. Researchers hope that their findings will eventually help people with PLCA, which is quite rare, lichen simplex and lichen planus, which are much more common, and possibly even people with other forms of itchy skin as well.


1. Breathnach SM (2004). Amyloid and the amyloidosis of the skin. In Burns T, Breathnach S, Cox C, Griffiths C, eds. Rook's Textbook of Dermatology Volume 3, (Oxford : Blackwell Scientific), pp.57.36–57.51. 2. K Arita, AP South, G Hans-Filho, TH Sakuma, J Lai-Cheong, S Clements, M Odashiro, DN Odashiro, G Hans-Neto, NR Hans, MV Holder, BS Bhogal, S Hartshorne, M Akiyama, H Shimizu, JA McGrath. Oncostatin M Receptor-? Mutations Underlie Familial Primary Localized Cutaneous Amyloidosis. American Journal of Human Genetics 2008; 82 (1): 73-80.

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