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Extending the molecular background of epidermolysis bullosa (EB) (Has 1)


Project details

Short lay summary

This project aims at extending the molecular background Epidermolysis bullosa (EB) by identifying disease-causing mutations in genetically unsolved cases. In the past 15 years, we have performed molecular testing in over 1500 patients suspected with EB and disclosed disease-causing mutations in the vast majority of them. However, the elucidation of the molecular basis of genetically unsolved cases requires “personalized” investigations comprising analyses on DNA, RNA and protein level which extend far beyond diagnostic procedures.

Both the urgency of high unmet medical need and the rapid advances in elucidating molecular mechanisms of EB have led to an advancement of biologically targeted therapies. However, their application requires a precise molecular diagnosis in every single case/family. Like in other studies, in our cohort of patients with EB simplex, the molecular basis of the disease remained unsolved in 18% of cases. Based on our preliminary work we have evidence for at least one new gene for EB simplex. In this project, we want to understand how the mutation found in this new gene leads to skin blistering. For this, we will study cells and skin equivalents in which the expression of the gene is diminished, and cells isolated from the patient. Furthermore, we want to identify mutations in two other families with distinctive clinical features in which mutations in known EB-genes were not found. Finally, the new findings will help to elucidate the molecular diagnosis in other unsolved cases. The new knowledge will benefit a large group of patients with EB simplex, which still lacks a precise diagnosis.


What did this project achieve?

A new EB gene and new mutational mechanisms are known in EB genes.

  1. We identified a new EB gene, KLHL24, coding for the protein kelch-like protein 24. Very little is known about this protein; it seems to be important for the function of the cytoskeleton of the skin cells. We found mutations in this new gene in 5% of all EB simplex cases. People carrying this mutation seem to develop extracutaneous features.
  2. We found unusual mutations in families with Kindler syndrome, EB simplex and dystrophic EB.
  3. We developed and validated a NGS based multi-gene panel for fast diagnosis of EB.

These results allow a better understanding of the causes of EB and may have an impact on the development of therapies.

Extension of the project.


University of Freiburg
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