title: Immunohistochemical, ultrastructural, and molecular features of Kindler syndrome distinguish it from dystrophic epidermolysis bullosa.
abstract: BACKGROUND
  Kindler syndrome is a rare, inherited skin disease characterized by acral bullae formation, fusion of fingers and toes, and generalized progressive poikiloderma. The purpose of this study was to clarify the nature of the bullous component of Kindler syndrome and to determine whether this inherited skin disorder represents a variant of dystrophic epidermolysis bullosa or a unique independent clinical entity.
  
  
  METHODS
  Two unrelated patients with Kindler syndrome were studied. Electron microscopy demonstrated marked duplication of the lamina densa, and clefts were observed in areas where the lamina densa was destroyed or obscured. Hemidesmosomes and anchoring fibrils showed normal features. Indirect immunofluorescence revealed normal linear labeling with antibodies against hemidesmosomal components (alpha 6 and beta 4 integrins, BPAG1, and BPAG2) and against anchoring filament components such as uncein, as detected by the 19-DEJ-1 monoclonal antibody. However, antibodies against the 3 respective laminin 5 chains, type IV collagen, and various type VII collagen epitopes (the aminoterminal NC1 domain, the central triple helical collagenous domain, and the carboxyterminal end of the triple helical collagenous domain) revealed a broad reticular staining pattern. Molecular screening of the type VII collagen gene (COL7A1) in the patients and their parents by heteroduplex analysis failed to detect any band shifts indicative of pathologic mutations.
  
  
  CONCLUSIONS
  These results suggest that the bullous component of Kindler syndrome is distinct from dystrophic epidermolysis bullosa caused by mutations in the type VII collagen gene. Additionally, the differential distribution patterns of uncein and laminin 5 in the patients' skin samples support the hypothesis that uncein and laminin 5 are different molecules.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: M
authors.initials: M
authors.lastname: Ban
authors.forename: Y
authors.initials: Y
authors.lastname: Kitajima
authors.forename: S
authors.initials: S
authors.lastname: Ishizaki
authors.forename: T
authors.initials: T
authors.lastname: Harada
authors.forename: L
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: J D
authors.initials: JD
authors.lastname: Fine
authors.forename: R
authors.initials: R
authors.lastname: Burgeson
authors.forename: A
authors.initials: A
authors.lastname: Kon
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: J
authors.initials: J
authors.lastname: Uitto
authors.forename: T
authors.initials: T
authors.lastname: Nishikawa
mesh_terms: D000328:Adult; D001485:Basement Membrane / Q000378:metabolism / Q000648:ultrastructure; D001706:Biopsy; D001768:Blister / Q000378:metabolism* / Q000473:pathology*; D003937:Diagnosis, Differential; D016108:Epidermolysis Bullosa Dystrophica / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005385:Fingers / Q000002:abnormalities; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011038:Rothmund-Thomson Syndrome / Q000378:metabolism* / Q000473:pathology*; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure*; D013576:Syndactyly / Q000378:metabolism / Q000473:pathology; D013577:Syndrome; D014034:Toes / Q000002:abnormalities