The genetic basis of epidermolytic hyperkeratosis: A disorder of differentiation-specific epidermal keratin genes

Jian Cheng*, Andrew J. Syder, Qian Chun Yu, Anthony Letal, Amy S. Paller, Elaine Fuchs

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

285 Scopus citations

Abstract

Epidermolytic hyperkeratosis (EH) is a skin disease characterized by keratin filament clumping and degeneration in terminally differentiating epidermal cells. We have discovered that the genetic basis for EH resides in mutations in differentiation-specific keratins. Two of six distinct incidences of EH had a keratin 10 (K10) point mutation in a highly conserved arginine. Remarkably, this same residue is mutated in the basal epidermal K14 in three incidences of another skin disease, epidermolysis bullosa simplex (EBS). By genetic engineering, gene transfection, and 10 nm filament assembly, we show that this mutation is functionally responsible for the keratin filament clumping that occurs in basal (EBS) or suprabasal (EH) cells. These studies strengthen the link between filament perturbations, cell fragility, and degeneration first established with EBS. They also suggest a correlation between filament disorganization and either cytokinesis or nuclear shape, giving rise to the seemingly binuceate cells typical of EH.

Original languageEnglish (US)
Pages (from-to)811-819
Number of pages9
JournalCell
Volume70
Issue number5
DOIs
StatePublished - Sep 4 1992

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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