Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion

MF Jonkman*, H Scheffer, R Stulp, HH Pas, Albertine Nijenhuis, K Heeres, K Owaribe, L Pulkkinen, J Uitto

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

217 Citations (Scopus)

Abstract

Mitotic gene conversion acting as reverse mutation has not been previously demonstrated in human. We report here that the revertant mosaicism of a compound heterozygous proband with an autosomal recessive genodermatosis, generalized atrophic benign epidermolysis bullosa, is caused by mitotic gene conversion of one of the two mutated COL17A1 alleles. Specifically, the maternal allele surrounding the mutation site on COL17A1 (1706delA) showed reversion of the mutation and loss of heterozygosity along a tract of at least 381 bp in revertant keratinocytes derived from clinically unaffected skin patches; the paternal mutation (R1226X) remained present in all cell samples. Revertant mosaicism represents a way of natural gene therapy.

Original languageEnglish
Pages (from-to)543-551
Number of pages9
JournalCell
Volume88
Issue number4
Publication statusPublished - 21-Feb-1997

Keywords

  • SOMATIC REVERSION SUPPRESSION
  • PEMPHIGOID ANTIGEN
  • MECHANISMS
  • COLLAGEN
  • EXPRESSION
  • PHENOTYPE
  • MUTATIONS
  • BP180
  • CELLS

Cite this