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Mutations in KRT10 in epidermolytic acanthoma
Author(s) -
Cheraghlou Shayan,
Atzmony Lihi,
Roy Simon F.,
McNiff Jennifer M.,
Choate Keith A.
Publication year - 2020
Publication title -
journal of cutaneous pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.597
H-Index - 75
eISSN - 1600-0560
pISSN - 0303-6987
DOI - 10.1111/cup.13664
Subject(s) - epidermolytic hyperkeratosis , biology , sanger sequencing , genomic dna , polymerase chain reaction , restriction fragment length polymorphism , microbiology and biotechnology , hyperkeratosis , pathology , genetics , mutation , gene , medicine
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.