|Title||Mutations in KRT10 in epidermolytic acanthoma.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Cheraghlou, S, Atzmony, L, Roy, SF, McNiff, JM, Choate, KA|
|Journal||J Cutan Pathol|
|Date Published||2020 Jun|
|Keywords||Acanthoma, Adult, Aged, Aged, 80 and over, Female, Genomics, Humans, Hyperkeratosis, Epidermolytic, Ichthyosis Bullosa of Siemens, Keratin-10, Keratins, Male, Middle Aged, Mutation, Skin Neoplasms, Whole Exome Sequencing|
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.
|Alternate Journal||J Cutan Pathol|
|PubMed Central ID||PMC7914398|
|Grant List||R01 AR071491 / NH / NIH HHS / United States |
U54 HG006504 / HG / NHGRI NIH HHS / United States
/ / Leon Rosenberg, M.D., Medical Student Research Fund in Genetics /
/ / Jane Danowski Weiss Family Foundation Fellowship /
R01 AR071491 / AR / NIAMS NIH HHS / United States