Epidermolysis Bullosa is a set of genetically inherited conditions affecting 1 in at least 17,000 of the population. A fault in a gene causes the skin to be extremely fragile. The layers of the skin do not adhere properly and painful widespread blisters occur very easily. Recessive dystrophic EB (RDEB) is one of the most severe forms with an estimated prevalence of 1 in 35,000.

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Development of DGGE Analysis of the Complete Collagen Type VII Gene for Rapid Molecular Diagnosis of All Forms of Dystrophic E B

Name of Researchers:		Dr H Scheffer -

Places of Research:		University of Groningen, Netherlands University Hospital Groningen, Netherlands

Approved by DebRA Medical & Scientific Advisory Panel:		28 June 1999

Budget approved by DebRA central Committee:		17 July 1999

Date Commenced		1 October '99 for 1 year

SUMMARY OF RESEARCH BEING UNDERTAKEN

Epidermolysis Bullosa is a set of genetically inherited conditions affecting 1 in at least 17,000 of the population. A fault in a gene causes the skin to be extremely fragile. The layers of the skin do not adhere properly and painful widespread blisters occur very easily. Recessive dystrophic EB (RDEB) is one of the most severe forms with an estimated prevalence of 1 in 35,000.

Patients affected by DEB suffer from loss of adhesion between the epidermis (outer layer of the skin) and the dermis (inner layer). This results in severe blistering of the skin and mucosa after mild trauma and is evident from birth. The extreme fragility of the skin results in traumatic blistering, wounds and scarring. These lead to increasing disfigurement, deformity and disability.

DEB is caused by abnormalities in the type VII collagen gene (COL7A1) encoding anchoring fibrils which form attachment structures playing a key role in the adhesion of the epidermis to the dermis. The majority of patients do not produce type VII collagen protein because they have inherited a deficient COL7A1 gene from each of their parents. The identification of COL7A1 as the defective gene in 1991 has allowed searches for mutations in patients and their family members to be carried out.

Identification of the COL7A1 defect in a given family has important implications for genetic counselling eg the detection of carriers, assessment of the mode of inheritance and early prenatal diagnosis (11 weeks of gestation) in affected families. It is also the first step towards genetic correction of the defect, since it enables the presence of a normal copy of the gene, following gene transfer, to be distinguished from the mutated copy.

The purpose of this project is the development of rapid and simple tests for DNA diagnosis of all forms of dystrophic EB. In these families, especially in those with a severely affected child, the demand for prenatal DNA tests is high. The structure of the gene causing dystrophic EB is extremely complex, which makes the identification of the mutations in a particular patient difficult. For this reason, DNA diagnosis of dystrophic EB is difficult. Currently, this labour intensive and expensive identification of the causative mutations is carried out in a few specialised research labs worldwide. Dr Scheffer proposes the development of an advanced technique, denaturing gradient gel electrophoresis (DGGE). This technique will make DNA diagnosis of these forms of EB more simple and more rapid. It will enable its implementation in routine DNA service laboratories.