title: Natural gene therapy in dystrophic epidermolysis bullosa.
abstract: BACKGROUND
  Dystrophic epidermolysis bullosa is a genetic blistering disorder caused by mutations in the type VII collagen gene, COL7A1. In revertant mosaicism, germline mutations are corrected by somatic events resulting in a mosaic disease distribution. This "natural gene therapy" phenomenon long has been recognized in other forms of epidermolysis bullosa but only recently in dystrophic epidermolysis bullosa.
  
  
  METHODS
  We describe a 21-year-old man with recessive dystrophic epidermolysis bullosa carrying the homozygous c.6508C>T (p.Gln2170X) nonsense mutation who reported an unaffected skin patch on his neck where blisters never had occurred. Immunofluorescent type VII collagen staining was normal in 80% of the unaffected skin biopsy; however, it was strongly reduced in the affected skin. In the unaffected skin, the somatic nucleotide substitution c.6510G>T reverted the germline nonsense codon to tyrosine (p.Gln2170Tyr), thereby restoring functional protein production.
  
  
  CONCLUSIONS
  Revertant mosaicism is considered rare in recessive dystrophic epidermolysis bullosa. However, it might be more common than previously anticipated because our patient is the third in whom revertant mosaicism was identified in a short period of time. The correction mechanism is different than that previously reported. Systematic examination of patients with recessive dystrophic epidermolysis bullosa, therefore, will likely reveal more patients with revertant patches. This is important because the natural gene therapy phenomenon may provide opportunities for revertant cell therapy.
authors: Department of Dermatology, University Medical Center Groningen, University of Groningen, the Netherlands. p.c.van.den.akker@umcg.nl
authors: Peter C
authors: PC
authors: van den Akker
authors: Miranda
authors: M
authors: Nijenhuis
authors: Gonnie
authors: G
authors: Meijer
authors: Robert M W
authors: RM
authors: Hofstra
authors: Marcel F
authors: MF
authors: Jonkman
authors: Anna M G
authors: AM
authors: Pasmooij
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D024143:Collagen Type VII / Q000032:analysis / Q000235:genetics*; D004252:DNA Mutational Analysis; D016108:Epidermolysis Bullosa Dystrophica / Q000235:genetics* / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008297:Male; D009030:Mosaicism; D055815:Young Adult
chemical_list: C569053:COL7A1 protein, human; D018389:Codon, Nonsense; D024143:Collagen Type VII