title: [Junctional epidermolysis bullosa. Identification of a new mutation in two Lebanese families].
abstract: BACKGROUND
  Junctional epidermolysis bullosa (JEB) represents a genetically heterozygous group of bullous disorders characterized by dermo-epidermal separation resulting from mutations affecting the main dermo-epidermal adhesion factor, laminin-5, its cellular receptor, integrin alpha6B4, or collagen XVII. We report the identification of a new mutation of LAMA3, encoding laminin-5 alpha3 subunit in two unrelated Lebanese families.
  
  
  METHODS
  Two female newborn, descending from 1st degree consanguineous marriages, presented a lethal form of EBJ-Herlitz. Histologic, ultrastructural and immunofluorescence studies were performed in order to ascertain the diagnosis and to direct genetic analysis. Mutation search was conducted through direct DNA sequencing of patients and ascendants.
  
  
  RESULTS
  Immunohistology of frozen skin samples revealed an extremely reduced immunoreactivity for the alpha3 laminin-5 subunit. The two patients were homozygous carriers (parents heterozygous) of a new missense mutation of LAMA3 gene (exon 32: 4300 insA) encoding the alpha3 subunit of laminin-5. Resulting messenger RNA, rapidly degraded, induced an extremely reduced synthesis of alpha3-polypeptide, truncated in its Cterminal domain.
  
  
  CONCLUSIONS
  LAMB3 gene recurrent mutations R636X and R42X account for about 50p. 100 of EBJ cases affecting Caucasians while mutation Q1083X, affecting the same gene, is recurrent in Arab populations. The newly identified mutation results in extremely reduced synthesis of alpha3 chain and truncation of its C-terminal domain, which is crucial for the intermolecular interactions of laminin-5. Our data are in accordance with recent reports suggesting geographical specificity of EBJ mutations linked to founder effects which are amplified by consanguineous marriages in genetically isolated populations. Otherwise, the observation of other unexplored cases of bullous dermatoses with early demise originating from the same region of the two families herein reported highlights the need for the implementation of a prenatal and postnatal diagnostic strategy regarding these genodermatoses. These studies should target LAMA3 and other genes involved in JEB too.
authors.affiliation: Service de Dermatologie, CHU Hôtel-Dieu de France, Beyrouth, Liban.
authors.forename: N
authors.initials: N
authors.lastname: Ayoub
authors.forename: R
authors.initials: R
authors.lastname: Tomb
authors.forename: A
authors.initials: A
authors.lastname: Charlesworth
authors.forename: G
authors.initials: G
authors.lastname: Meneguzzi
mesh_terms: D003241:Consanguinity; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007797:Laminin / Q000235:genetics*; D007861:Lebanon; D010375:Pedigree
chemical_list: D007797:Laminin; C095567:laminin alpha 3; D004247:DNA