Scientists have identified genetic changes responsible for the rare skin condition, ichthyosis with confetti (IWC). They also discovered that skin cells from patients with IWC can eliminate the genetic mutation that causes the disease - resulting in its characteristic patchy disappearance, as areas of normal skin gradually appear.
The team from Yale Medical School in the US studied cells from IWC patients, both from affected and healthy areas of skin. They sequenced DNA from the cells and located a gene which was mutated in affected cells, but not healthy ones. The gene, KRT10, makes a keratin protein which maintains the integrity of skin cells. In cells with a mutated KRT10 gene, the protein was located in a different area of the cell.
They suggest that each healthy patch of skin is caused by a single mitotic recombination in a skin stem cell. The recombination creates a cell containing two healthy copies of KRT10 and with the mutation gone, the stem cell produces healthy skin cells.
During mitotic recombination, dividing maternal and paternal chromosomes exchange DNA. The process is also linked to cancer as it can allow a once recessive cancer-causing mutation to suddenly take effect.
Other processes, such as random mutation, are far too rare to cause the thousands of healthy skin patches seen in IWC patients. However, mitotic recombination is also uncommon and so the authors suggest something must be driving the process.
It could be that natural selection is occurring under the skin and the healthy cells compete to survive. Another possibility is that as mitotic recombination is known to occur at varying frequencies along the genome, KRT10 could be at a hot spot. Alternatively the mutated protein itself could be driving the process as it builds up in the nucleus of the cell.
The researchers suggest that knowing that this type of mutation can frequently revert means that they may be able to develop treatments for other genetic diseases, which mimic the process.
The study is published in the 26th August edition of Science Express.