Mutations in KRT10 in epidermolytic acanthoma

Shayan Cheraghlou, Lihi Atzmony, Simon F. Roy, Jennifer M. McNiff, Keith A. Choate*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Epidermolytic acanthoma (EA) is a rare acquired lesion demonstrating a characteristic histopathological pattern of epidermal degeneration referred to as epidermolytic hyperkeratosis (EHK). On histopathological analysis, EA appears nearly identical to inherited EHK-associated dermatoses such as epidermolytic ichthyosis and ichthyosis bullosa of Siemens. While it has been speculated that EA is caused by mutations in KRT10, KRT1, or KRT2 found in these inherited dermatoses, none have yet been identified. Herein, we aim to identify the contributions of keratin mutations to EA. Methods: Using genomic DNA extracted from paraffin-embedded samples from departmental archives, we evaluated a discovery cohort using whole-exome sequencing (WES) and assessed remaining samples using Sanger sequencing screening and restriction fragment length polymorphism (RFLP) analysis. Results: DNA from 16/20 cases in our sample was of sufficient quality for polymerase chain reaction amplification. WES of genomic DNA from lesional tissue revealed KRT10 c.466C > T, p.Arg156Cys mutations in 2/3 samples submitted for examination. RFLP analysis of these samples as well as eight additional samples confirmed the mutations identified via WES and identified four additional cases with Arg156 mutations. In sum, 6/11 screened cases showed hotspot mutation in KRT10. Conclusions: Hotspot mutations in the Arg156 position of KRT10, known to cause epidermolytic ichthyosis, also underlie EA.

Original languageEnglish
Pages (from-to)524-529
Number of pages6
JournalJournal of Cutaneous Pathology
Volume47
Issue number6
DOIs
StatePublished - 1 Jun 2020
Externally publishedYes

Funding

FundersFunder number
Yale Center for Mendelian GenomicsU54 HG006504
National Institutes of HealthR01 AR071491
National Human Genome Research InstituteU54HG006504

    Keywords

    • KRT10
    • epidermolytic acanthoma
    • keratin 10
    • mutations
    • whole-exome sequencing

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