Tags

Type your tag names separated by a space and hit enter

Recombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma.
J Dermatol Sci. 2020 Feb; 97(2):94-100.JD

Abstract

Revertant mosaicism refers to a condition in which a pathogenic germline mutation is spontaneously corrected in somatic cells, resulting in the presence of two or more cell populations with different genotypes in an organism arising from a single fertilized egg. If the revertant cells are clonally expanded due to a survival advantage over the surrounding mutant cells, patients benefit from this self-healing phenomenon which leads to the development of milder-than-expected clinical phenotypes; in genetic skin diseases, patients with revertant mosaicism present with small islands of healthy skin. To date, revertant mosaicism has been reported in ∼50 genetic diseases involving the skin, blood, liver, muscle, and brain. In this review, I briefly summarize current knowledge on revertant mosaicism in two particular skin diseases, ichthyosis with confetti (IWC) and loricrin keratoderma (LK), both of which develop numerous revertant skin patches. Notably, homologous recombination (HR) is the only mechanism underlying the reversion of pathogenic mutations in IWC and LK, and this was identified following the analysis of ∼50 revertant epidermis samples. All the samples showed long-tract loss of heterozygosity (LOH) that originated at regions centromeric to pathogenic mutations and extended to the telomere of the mutation-harboring chromosomes. Elucidating the molecular mechanisms underlying revertant mosaicism in IWC and LK-especially how mutant proteins induce long-tract LOH-would potentially expand the possibility of manipulating HR to induce the reversion of disease-causing mutations and help devising novel therapies not only for IWC and LK but also for other intractable genetic diseases.

Authors+Show Affiliations

Department of Dermatology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan. Electronic address: nomura@huhp.hokudai.ac.jp.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

31928837

Citation

Nomura, Toshifumi. "Recombination-induced Revertant Mosaicism in Ichthyosis With Confetti and Loricrin Keratoderma." Journal of Dermatological Science, vol. 97, no. 2, 2020, pp. 94-100.
Nomura T. Recombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma. J Dermatol Sci. 2020;97(2):94-100.
Nomura, T. (2020). Recombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma. Journal of Dermatological Science, 97(2), 94-100. https://doi.org/10.1016/j.jdermsci.2019.12.013
Nomura T. Recombination-induced Revertant Mosaicism in Ichthyosis With Confetti and Loricrin Keratoderma. J Dermatol Sci. 2020;97(2):94-100. PubMed PMID: 31928837.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Recombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma. A1 - Nomura,Toshifumi, Y1 - 2019/12/31/ PY - 2019/12/22/received PY - 2019/12/26/revised PY - 2019/12/26/accepted PY - 2020/1/14/pubmed PY - 2020/1/14/medline PY - 2020/1/14/entrez KW - Homologous recombination KW - Ichthyosis with confetti KW - Loricrin keratoderma KW - Loss of heterozygosity KW - Revertant mosaicism SP - 94 EP - 100 JF - Journal of dermatological science JO - J. Dermatol. Sci. VL - 97 IS - 2 N2 - Revertant mosaicism refers to a condition in which a pathogenic germline mutation is spontaneously corrected in somatic cells, resulting in the presence of two or more cell populations with different genotypes in an organism arising from a single fertilized egg. If the revertant cells are clonally expanded due to a survival advantage over the surrounding mutant cells, patients benefit from this self-healing phenomenon which leads to the development of milder-than-expected clinical phenotypes; in genetic skin diseases, patients with revertant mosaicism present with small islands of healthy skin. To date, revertant mosaicism has been reported in ∼50 genetic diseases involving the skin, blood, liver, muscle, and brain. In this review, I briefly summarize current knowledge on revertant mosaicism in two particular skin diseases, ichthyosis with confetti (IWC) and loricrin keratoderma (LK), both of which develop numerous revertant skin patches. Notably, homologous recombination (HR) is the only mechanism underlying the reversion of pathogenic mutations in IWC and LK, and this was identified following the analysis of ∼50 revertant epidermis samples. All the samples showed long-tract loss of heterozygosity (LOH) that originated at regions centromeric to pathogenic mutations and extended to the telomere of the mutation-harboring chromosomes. Elucidating the molecular mechanisms underlying revertant mosaicism in IWC and LK-especially how mutant proteins induce long-tract LOH-would potentially expand the possibility of manipulating HR to induce the reversion of disease-causing mutations and help devising novel therapies not only for IWC and LK but also for other intractable genetic diseases. SN - 1873-569X UR - https://www.unboundmedicine.com/medline/citation/31928837/Recombination-induced_revertant_mosaicism_in_ichthyosis_with_confetti_and_loricrin_keratoderma L2 - https://linkinghub.elsevier.com/retrieve/pii/S0923-1811(19)30419-0 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.