Natural gene therapy may occur in all patients with generalized non-Herlitz junctional epidermolysis bullosa with COL17A1 mutations.
Mutations in the type XVII collagen gene (COL17A1) result in the blistering disorder non-Herlitz junctional epidermolysis bullosa (JEB-nH). The incidence of revertant mosaicism, also called "natural gene therapy", was identified in a cohort of 14 patients with JEB-nH caused by COL17A1 mutations in the Netherlands. Five different in vivo reversions, all correcting the germ-line COL17A1 mutation c.2237delG in exon 30, were found in four mosaic JEB-nH patients. The correcting DNA changes involved a wide variety of somatic mutations, from which an indel mutation (c.2228-101_2263+70delins15) and a large deletion of 2,165 base pairs (c.2227+153_2336-318del) have not been previously observed in patients with revertant mosaicism. Our results show that there is no preference for a repair mechanism. Moreover, revertant mosaicism was confirmed on a DNA level in 6 out of 10 generalized JEB-nH patients. Further, photo-material and clinical history of the other four generalized JEB-nH patients demonstrated that each patient has revertant skin patches. In contrast, revertant mosaicism was not detected in the four localized JEB-nH patients. The fact that so many, if not all, generalized JEB-nH COL17A1 patients have revertant patches offers opportunities for cell therapies in which the patient's own naturally corrected cells are used as a source.
Department of Dermatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. a.m.g.pasmooij@derm.umcg.nl
Anna M G
AM
Pasmooij
Miranda
M
Nijenhuis
Renske
R
Brander
Marcel F
MF
Jonkman
D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004260:DNA Repair; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015316:Genetic Therapy; D018095:Germ-Line Mutation; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D024041:Non-Fibrillar Collagens / Q000235:genetics* / Q000378:metabolism; D012075:Remission, Spontaneous; D017422:Sequence Analysis, DNA; D000097805:Collagen Type XVII
D001324:Autoantigens; D024041:Non-Fibrillar Collagens; D000097805:Collagen Type XVII