title: Identification of the LAMB3 hotspot mutation R635X in a Hungarian case of Herlitz junctional epidermolysis bullosa.
abstract: The Herlitz type of junctional epidermolysis bullosa (H-JEB) is a severe blistering disease affecting the skin and mucous membranes, which is usually lethal within the first year of life. The laminin 5 genes have been implicated as candidate genes for most patients with H-JEB. Recently, two hotspot mutations were delineated in the LAMB3 gene, known as R42X and R635X, and have been noted in over 50% of mutant LAMB3 alleles. Here, we present a case of H-JEB of Hungarian origin with a neonatal lethal outcome. Monoclonal antibody staining showed a lack of expression of the laminin 5 beta 3 chain, as a possible result of a mutation in one of the laminin 5 genes. Screening of the family identified the previously described mutation R635X in exon 14 of LAMB3 in each of the parents and one healthy sibling in the heterozygous form, while proband was homozygous for R635X, and the other sibling proved to be genotypically normal. These results underscore the widespread prevalence of R635X in H-JEB cases from around the world.
authors.affiliation: Department of Dermatology, Semmelweis Medical University, Budapest, Hungary.
authors.forename: P B
authors.initials: PB
authors.lastname: Cserhalmi
authors.forename: A
authors.initials: A
authors.lastname: Horvath
authors.forename: V
authors.initials: V
authors.lastname: Boros
authors.forename: Z
authors.initials: Z
authors.lastname: Sapi
authors.forename: M
authors.initials: M
authors.lastname: Kormendi
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: S
authors.initials: S
authors.lastname: Karpati
mesh_terms: D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D017809:Fatal Outcome; D006801:Humans; D006814:Hungary; D007231:Infant, Newborn; D007797:Laminin / Q000172:deficiency / Q000235:genetics; D008297:Male; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012867:Skin / Q000473:pathology
chemical_list: D007797:Laminin