title: Autosomal dominant junctional epidermolysis bullosa.
abstract: BACKGROUND
  Epidermolysis bullosa (EB) encompasses a heterogeneous group of inherited skin disorders associated with trauma-induced blistering. The junctional forms of EB (JEB), Herlitz JEB, non-Herlitz JEB and JEB associated with pyloric atresia have all been attributed to autosomal recessive inheritance. We describe a 7-year-old girl with defective dental enamel, trauma-induced blistering and subsequent scarring. Her mother, a carrier of the mutation p.G627V in the collagen XVII gene (COL17A1) had evidence of hypoplastic dental enamel without skin blistering. Her grandmother had non-Herlitz JEB as a result of a compound heterozygous mutation in COL17A1 (p.G627V and c.3514ins25).
  
  
  OBJECTIVE
  To explore the molecular, ultrastructural and immunofluorescence findings of the first case of dominant JEB.
  
  
  METHODS
  Mutational analysis of COL17A1 was performed on the proband's genomic DNA. In addition, transmission electron microscopy and immunofluorescence microscopy were performed on a nonlesional skin biopsy from the proband and an unrelated healthy control.
  
  
  RESULTS
  Direct sequencing revealed a heterozygous glycine substitution mutation, p.G627V, in COL17A1. No discernible morphological abnormalities were found on transmission electron microscopy; however, immunofluorescence microscopy revealed findings of an altered distribution pattern for type XVII collagen epitopes close to the dermal-epidermal junction.
  
  
  CONCLUSIONS
  This report describes the first case of dominant JEB. Although some heterozygous mutations in COL17A1 are known to cause dental abnormalities none were associated with skin fragility. The dominant-negative interference between the proband's mutated type XVII collagen and the wild-type allele appears to render the skin prone to trauma-induced blister formation. Alternatively, other undisclosed modifying genetic or epigenetic factors might explain why the patient gets blistering whereas her mother, who has the same COL17A1 mutation, has no skin fragility.
authors.affiliation: Genetic Skin Disease Group, St John's Institute of Dermatology, King's College London, Guy's Campus, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Almaani
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: P J C
authors.initials: PJ
authors.lastname: Dopping-Hepenstal
authors.forename: P A
authors.initials: PA
authors.lastname: Lovell
authors.forename: J E
authors.initials: JE
authors.lastname: Lai-Cheong
authors.forename: R M
authors.initials: RM
authors.lastname: Graham
authors.forename: J E
authors.initials: JE
authors.lastname: Mellerio
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D001768:Blister / Q000209:etiology; D002648:Child; D004252:DNA Mutational Analysis; D003743:Dental Enamel / Q000002:abnormalities* / Q000473:pathology; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000473:pathology; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008856:Microscopy, Fluorescence; D024041:Non-Fibrillar Collagens / Q000235:genetics*; D010375:Pedigree; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII