A Professor at the University of Dundee has just discovered the gene that causes two inherited skin disorders allowing rapid and highly accurate DNA-based diagnosis.
Professor Irwin McLean at the University of Dundee's Medical School has discovered the gene that causes Kindler syndrome, a rare genetic condition that causes skin blistering in infancy similar to epidermolysis bullosa (EB) but also causes premature ageing of the skin.
For sufferers of Kindler syndrome this discovery will lead to new therapies that will treat the disease.
The Kindler syndrome gene was identified by scanning the entire human genome for a region shared by Kindler syndrome patients but was absent in their normal relatives. Analysis of the genes in this region resulted in the discovery of a novel gene that makes a new class of protein in the skin. Further analysis showed that the protein, called kindlin-1, contributes to the structure of the skin and explains the blistering in patients. Professor McLean thinks that the same protein is also likely to be involved in cell signalling which might explain the premature aging symptom. Further research into this new protein may help unravel the normal skin ageing process.
Interestingly for the researchers, they found the gene in other species including primitive worms which use the protein to attach their skin to their underlying muscle.
Professor McLean and his team discovered this potentially revolutionary gene as part of an international consortium to identify the cause of Kindler syndrome including the University of Dundee, the University of California, San Franciscoand Professor John McGrath's group, St Thomas's Hospital, London. The Dundee and London groups are now continuing the project to better understand the function of this new protein in this distressing condition and skin ageing in general.
The second discovery is the identification of the gene which causes laryngo-onycho-cutaneous (LOC) syndrome a rare genetic condition quite commonly suffered by Pakistanis.
The syndrome is characterised by abnormal wound healing in the skin and other tissues including the eye, the larynx and the nails where patients get a build up of granulation tissue which is commonly seen in patients with chronic leg ulcers and rheumatoid arthritis. LOC patients suffer skin lesions which are very slow to heal and the granulation tissue also causes closure of the larynx leading to difficulties in breathing. Usually patients require a permanent tracheotomy by age ten.
By scanning the human genome map, Irwin and his team identified a region shared by all LOC patients which was absent in their unaffected relatives. The gene, called laminin alpha-3 is a gene that is already known but the team discovered that it is twice its previously reported size and makes three distinct proteins laminin alpha-3a, alpha 3b1 and alpha 3b2. The defect within this gene in LOC patients affects only a small part of one of these proteins (alpha 3a) and the defect itself represents a completely novel genetic mechanism explaining the rarity of the condition outside the Pakistani population.
The Dundee group are going on to study these mechanisms in more detail, with the aim of developing therapies for LOC syndrome and importantly other conditions including venous leg ulcers and rheumatoid arthritis.
Contact Professor Irwin McLean 01382 425618 (direct line)
By Jenny Marra, Head of Press 01382 344910 j.m.marra@dundee.ac.uk