DNA based molecular analysis in the rapid diagnosis of Herlitz junctional epidermolysis bullosa

The junctional form of epidermolysis bullosa (JEB) is an inherited blistering disease in which blisters occur at the level of the lamina lucida in the cutaneous basement membrane zone. Specific mutations have been detected in the genes encoding different components of the hemidesmosomal-anchoring filament complex. In the recessively inherited lethal (Herlitz) type of JEB (H-JEB), typically nonsense mutations or insertions or deletions are present on both alleles of any of the three genes encoding the polypeptide subunits of the anchoring filament protein, laminin 5. In this study, we searched for mutations in a proband who presented at birth with severe and extensive blistering. We detected a novel 1 bp deletion and a previously reported hotspot mutation (R635X) in the LAMB3 gene. This mutation combination established the diagnosis of H-JEB in this case, in which attempted diagnosis by skin biopsy had failed. The molecular analysis was performed shortly after birth while the patient was admitted to the intensive care unit, and the definitive molecular diagnosis allowed the parents and physicians to devise management plans.