Epidermolysis Bullosa - Mutation Characterisation

Currently, the Queensland branch of the Dystrophic Epidermolysis Bullosa Research Association of Australia (DEBRA-A) is funding characterisation of mutations associated with Epidermolysis Bullosa (EB). Funding so far has provided a computer, a colour printer, and small lab equipment, and over $15,000 for the biological reagents required for this project. The research associated with this service is being done in the Division of Chemical Pathology, Queensland Health Pathology Service, Royal Brisbane Hospital and is headed by Sandra Klingberg.

Mutational analysis is possible in the three major categories - simplex, junctional, and dystrophic. Each of these forms is associated with mutations in different genes. For example, dystrophic forms of EB are associated with mutations in the Collagen 7 gene (COL7A1), the Simplex forms are associated with the Keratin genes (KRT14 & KRT5) and the junctional forms are associated with Laminin and Integrin genes (for example LAMB3 & ITGB4). (Go to About EB)

The establishment of this diagnostic service is being undertaken in three stages:

1. Development of PCR based methods to specifically screen for mutations that have already been described in the literature, associated with specific forms of EB.
2. Development of PCR based methods to sequence all exons of the various genes associated with EB, to look for new mutations.
3. Development of general screening techniques for rapid detection of mutations in new EB patients.

However, mutation characterisation is only part of the picture in providing an accurate diagnosis. Before mutation studies can be done, the correct subtype of EB - simplex, junctional, or dystrophic - must be known. While the clinical presentation and family history contribute to this picture, often vital information from electron microscopy and immunofluorescence mapping from a skin biopsy is required. This information confirms the subtype of EB and then allows the researcher to target the correct gene for the mutation characterisation.

The electron microscopy work is performed in Anatomical Pathology at Royal Brisbane Hospital. DR. DEDEE MURRELL M.D., a dermatologist at St George Hospital Kogarah, NSW, performs the immunofluorescence mapping. Both of these specialists interact closely with the Queensland Health Pathology Service to assist in the accurate diagnosis of the correct subtype of EB.