REVERTANT MOSAICISM IN EPIDERMOLYSIS-BULLOSA CAUSED BY MITOTIC GENE CONVERSION

Mitotic gene conversion acting as reverse mutation has not been previo usly demonstrated in human. We report here that the revertant mosaicis m of a compound heterozygous proband with an autosomal recessive genod ermatosis, generalized atrophic benign epidermolysis bullosa, is cause d by mitotic gene conversion of one of the two mutated COL17A1 alleles . Specifically, the maternal allele surrounding the mutation site on C OL17A1 (1706delA) showed reversion of the mutation and loss of heteroz ygosity along a tract of at least 381 bp in revertant keratinocytes de rived from clinically unaffected skin patches; the paternal mutation ( R1226X) remained present in all cell samples. Revertant mosaicism repr esents a way of natural gene therapy.