title: Localized and generalized forms of blistering in junctional epidermolysis bullosa due to COL17A1 mutations in the Netherlands.
abstract: BACKGROUND
  Mutations in the gene COL17A1 coding for type XVII collagen cause non-Herlitz junctional epidermolysis bullosa (nH-JEB).
  
  
  OBJECTIVE
  Here we give an overview of the genotype-phenotype correlation in 12 patients from the Netherlands with type XVII collagen-deficient nH-JEB.
  
  
  METHODS
  Family and personal history and clinical presentation were recorded from each patient, and skin biopsies of intact and bullous skin were taken for immunofluorescence and electron microscopy. The mutations were identified by analysing the patient's DNA isolated from peripheral blood cells.
  
  
  RESULTS
  DNA analysis identified five novel deletions: 1284delA, 1365delC, 3236delT, 3600-3601delCT and 4425delT. Interestingly, we identified a new patient, homozygous for 4425delT, with an exceptionally mild blistering phenotype. All together, three patients had more localized blistering confined to hands, lower legs and face, absent or very mild nail dystrophy, normal primary hair and sparse secondary hair. Nine patients had generalized blistering, nail dystrophy, sparse primary and absent secondary hair. All 12 patients had amelogenesis imperfecta (enamel pitting). Immunofluorescence (IF) antigen mapping with monoclonal antibodies 1A8C and 1D1 that bind to type XVII collagen, but not to its 97-kDa fragment was completely negative in patients with generalized blistering, whereas reduced in patients with localized blistering.
  
  
  CONCLUSIONS
  Our data reveal that in patients with COL17A1 mutations a localized nH-JEB phenotype can be differentiated from a generalized nH-JEB phenotype by IF antigen mapping. The data are important for genetic counselling at early age when the clinical phenotype is not yet clear.
authors.affiliation: Centre for Blistering Diseases, Department of Dermatology, University Medical Centre Groningen, University of Groningen, Hanzeplein-1, Groningen, The Netherlands.
authors.forename: A M G
authors.initials: AM
authors.lastname: Pasmooij
authors.forename: H H
authors.initials: HH
authors.lastname: Pas
authors.forename: G H L
authors.initials: GH
authors.lastname: Jansen
authors.forename: H H
authors.initials: HH
authors.lastname: Lemmink
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics* / Q000276:immunology; D001768:Blister / Q000235:genetics / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016109:Epidermolysis Bullosa, Junctional / Q000235:genetics* / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009154:Mutation; D009426:Netherlands; D024041:Non-Fibrillar Collagens / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D014421:Turkey / Q000208:ethnology; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII