Back mutation

Reverse mutation is understood to be a mutation that phenotypically and genotypically converts a mutated genotype back to the wild type (to the original genetic type), i.e. normalizes it, by exactly restoring the original nucleotide sequence. In the case of focally back-mutated skin, a normal skin appearance is again seen in a pathological environment, at these sites.

Back mutations can be distinguished from compensating mutations by crossing "back mutant × wild type". If a back mutation is present, the entire progeny corresponds to the wild type, whereas if a compensating mutation is present, the mutants reappear in the progeny due to recombination.

An organism, or as in the case of reverse mosaics, a cell clone, that shows the original phenotype (usually of the wild type) due to a reverse mutation is called a reverse mutant or revertant.

The phenomenon of back mutaion has been demonstrated, for example, in epidermolysis bullosa. It is likely that such back mutant areas also exist in other autosomal recessive genodermatoses, for example in xeroderma pigmentosum, but have so far remained unnoticed.The phenomenon represents, so to speak, a kind of natural gene therapy .

Furthermore, reversion mutations play a role, for example, in the development of therapy resistance to chemotherapeutic agents of breast and ovarian carcinomas as well as in pancreatic and prostate carcinomas. Tumors in these patients tend to lose both copies of the wild-type BRCA gene, making them particularly sensitive to platinum drugs and poly(ADP-ribose) polymerase inhibitors (PARPi), the therapies of choice in these diseases.

Pharmacological inhibition of DNA end-joining repair pathways improves drug treatment outcomes by preventing the acquisition of reversion mutations in BRCA genes, for example (Tobalina L et al. 2021).

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