IDENTIFICATION OF THE LAMB3 HOTSPOT MUTATION R635X IN A HUNGARIAN CASE OF HERLITZ JUNCTIONAL EPIDERMOLYSIS-BULLOSA

The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a seve re blistering disease affecting the skin and mucous membranes, which i s usually lethal within the first year of life. The laminin 5 genes ha ve been implicated as candidate genes for most patients with H-JEB. Re cently, two hotspot mutations were delineated in the LAMB3 gene, known as R42X and R635X, and have been noted in over 50% of mutant LAMB3 al leles. Here, we present a case of H-JEB of Hungarian origin with a neo natal lethal outcome. Monoclonal antibody staining showed a lack of ex pression of the laminin 5 beta 3 chain, as a possible result of a muta tion in one of the laminin 5 genes. Screening of the family identified the previously described mutation R635X in exon 14 of LAMB3 in each o f the parents and one healthy sibling in the heterozygous form, while proband was homozygous for R635X, and the other sibling proved to be g enotypically normal. These results underscore the widespread prevalenc e of R635X in H-JEB cases from around the world.