Mitotic Recombination in Patients with Ichthyosis Causes Reversion of Dominant Mutations in KRT10

Abstract

Gaining from a Loss Mitotic recombination can cause a cell carrying heterozygous mutations in a tumor suppressor gene to lose the wild-type copy of the gene, setting the cell on the pathway to uncontrolled growth. But can mitotic recombination have beneficial effects in other settings—that is, lead to phenotypic correction of a diseased cell by facilitating loss of the disease-causing mutation? Choate et al. (p. 94 , published online 26 August; see the Perspective by Davis and Candotti ) now find evidence for this type of event in a rare skin disease called ichthyosis with confetti (IWC). Patients with IWC display severe scaling of the skin but have widespread patches of normal skin that reflect clonal expansion of revertant cells. The revertant cells showed loss of heterozygosity on chromosome 17q and, as a result of mitotic recombination, these cells selectively lost dominant disease-causing mutations in the keratin 10 gene ( KRT10 ), but retained the wild-type copy of the gene.