Mutations in KRT10 in epidermolytic acanthoma.
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.
['Cheraghlou|Shayan|S|https://orcid.org/0000-0003-4382-7828', 'Atzmony|Lihi|L|', 'Roy|Simon F|SF|https://orcid.org/0000-0002-5444-0349', 'McNiff|Jennifer M|JM|', 'Choate|Keith A|KA|']
D049309:Acanthoma D000328:Adult D000368:Aged D000369:Aged, 80 and over D005260:Female D023281:Genomics D006801:Humans D017488:Hyperkeratosis, Epidermolytic D053560:Ichthyosis Bullosa of Siemens D053550:Keratin-10 D007633:Keratins D008297:Male D008875:Middle Aged D009154:Mutation D012878:Skin Neoplasms D000073359:Whole Exome Sequencing
mutations KRT10 epidermolytic acanthoma whole-exome sequencing keratin 10