ABSTRACT OF RESEARCH BEING UNDERTAKEN

Detection of mutations in patients and familes with EB is a prerequisite for gene therapy since the precise genetic defect must be identified before gene correction or other forms of gene supplementation can be considered. Knowing the gene defect is also very reassuring for the family and, importantly, it allows precise genetic counselling and predictive testing for future pregnancies in the family. Despite the fact that the gene causing EBS, the most common form of EB, has been known since 1991, more than 20% of patients with this disorder do not have detectable mutations in genes encoding keratins 5 and 14 (K5 and K14). This represents about 1,000 patients in the UK alone.

This project tackles that problem. A group of EBS patients lacking K5 and K14 mutations will be re-evaluated clinically to look for subtle signs that might indicate alternative diagnoses and to obtain fresh DNA for analysis. A number of newly developed methods for detecting unusual mutations will be applied to these patient samples. New regions of candidate genes will be sought out, again using methods that have only become available recently. There is also recent evidence that there may be a clinical overlap between EBS and other keratin disorders or other forms of EB. These genes will also be thoroughly screened.

Any new genes or new types of mutations found will go into immediate use in the UK-wide NHS screening service for EBS established in Dundee and will, therefore, immediately start to provide EBS families with improved diagnosis, genetic counselling and reassurance about future pregnancies.