Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti

Keith A. Choate*, Yin Lu, Jing Zhou, Peter M. Elias, Samir Zaidi, Amy S. Paller, Anita Farhi, Carol Nelson-Williams, Debra Crumrine, Leonard M. Milstone, Richard P. Lifton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Widespread reversion of genetic disease is rare; however, such events are particularly evident in some skin disorders in which normal clones develop on a background of affected skin. We previously demonstrated that mutations in keratin 10 (KRT10) cause ichthyosis with confetti (IWC), a severe dominant disorder that is characterized by progressive development of hundreds of normal skin spots via revertant mosaicism. Here, we report on a clinical and histological IWC subtype in which affected subjects have red, scaly skin at birth, experience worsening palmoplantar keratoderma in childhood, and develop hundreds of normal skin spots, beginning at around 20 years of age, that increase in size and number over time. We identified a causal de novo mutation in keratin 1 (KRT1). Similar to IWC-causing KRT10 mutations, this mutation in KRT1 resulted in a C-terminal frameshift, replacing 22 C-terminal amino acids with an alternate 30-residue peptide. Mutant KRT1 caused partial collapse of the cytoplasmic intermediate filament network and mislocalized to the nucleus. As with KRT10 mutations causing IWC, reversion of KRT1 mutations occurred via mitotic recombination. Because reversion is not observed with other diseasecausing keratin mutations, the results of this study implicate KRT1 and KRT10 C-terminal frameshift mutations in the high frequency of revertant mosaicism in IWC.

Original languageEnglish (US)
Pages (from-to)1703-1707
Number of pages5
JournalJournal of Clinical Investigation
Issue number4
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Frequent somatic reversion of KRT1 mutations in ichthyosis with confetti'. Together they form a unique fingerprint.

Cite this