We identified 72 new or recurrent mutations. Some of these data were also used to undertake DNA-based prenatal diagnosis in 12 families at risk for recurrence of severe forms of JEB or RDEB. To extend genotype-phenotype correlation, we have focused on further investigation of some exceptions to the usual paradigm.

For example, some patients with nonsense mutations on both alleles of either COL7A1 or laminin 5 genes appear to have less severe features than most. In such cases, we are assessing alterations in RNA processing such as skipping of exons containing such mutations or alternative splicing. Hopefully, we will be able to extend our understanding of genotype-phenotype correlation and determine just what clinical information can safely be predicted from analysis of genomic DNA alone. Such data will be extremely useful in counselling and managing patients in the clinic.

Overall, this grant-funded activity is providing a stepping-stone from a clinically orientated research activity towards laboratory service work, funded as part of a Supraregional diagnostic centre at St Thomas’ Hospital, which is scheduled to become active towards the latter part of 2002.

John McGrath

Professor of Molecular Dermatology

St John’s Institute of Dermatology