Natural Gene Therapy May Occur in All Patients with Generalized Non-Herlitz Junctional Epidermolysis Bullosa with COL17A1 Mutations

Anna M. G. Pasmooij*, Albertine Nijenhuis, Renske Brander, Marcel F. Jonkman

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

50 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1374-1383
Number of pages10
JournalJournal of Investigative Dermatology
Volume132
Issue number5
DOIs
Publication statusPublished - May-2012

Keywords

  • REVERTANT MOSAICISM
  • MESSENGER-RNA
  • XVII COLLAGEN
  • STEM-CELLS
  • MILD FORM
  • SIMPLEX
  • RECOMBINATION
  • AUTOANTIGEN
  • REVERSION
  • LOCUS

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