title: Revertant mosaicism in epidermolysis bullosa caused by mitotic gene conversion.
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.
authors.affiliation: Department of Dermatology, University Hospital Groningen, The Netherlands.
authors.forename: M F
authors.initials: MF
authors.lastname: Jonkman
authors.forename: H
authors.initials: H
authors.lastname: Scheffer
authors.forename: R
authors.initials: R
authors.lastname: Stulp
authors.forename: H H
authors.initials: HH
authors.lastname: Pas
authors.forename: M
authors.initials: M
authors.lastname: Nijenhuis
authors.forename: K
authors.initials: K
authors.lastname: Heeres
authors.forename: K
authors.initials: K
authors.lastname: Owaribe
authors.forename: L
authors.initials: L
authors.lastname: Pulkkinen
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D003094:Collagen / Q000235:genetics; D004820:Epidermolysis Bullosa / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005785:Gene Conversion; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D010641:Phenotype; D017422:Sequence Analysis, DNA; D012867:Skin / Q000473:pathology
chemical_list: D003094:Collagen