Mutations in KRT10 in epidermolytic acanthoma.
KRT10
epidermolytic acanthoma
keratin 10
mutations
whole-exome sequencing
Journal
Journal of cutaneous pathology
ISSN: 1600-0560
Titre abrégé: J Cutan Pathol
Pays: United States
ID NLM: 0425124
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
13
09
2019
revised:
08
01
2020
accepted:
24
01
2020
pubmed:
12
2
2020
medline:
4
3
2021
entrez:
12
2
2020
Statut:
ppublish
Résumé
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. 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. 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. Hotspot mutations in the Arg156 position of KRT10, known to cause epidermolytic ichthyosis, also underlie EA.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
Hotspot mutations in the Arg156 position of KRT10, known to cause epidermolytic ichthyosis, also underlie EA.
Identifiants
pubmed: 32045015
doi: 10.1111/cup.13664
pmc: PMC7914398
mid: NIHMS1673712
doi:
Substances chimiques
KRT10 protein, human
0
Keratin-10
147785-83-9
Keratins
68238-35-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
524-529Subventions
Organisme : NIH HHS
ID : R01 AR071491
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006504
Pays : United States
Organisme : Leon Rosenberg, M.D., Medical Student Research Fund in Genetics
Organisme : Jane Danowski Weiss Family Foundation Fellowship
Organisme : NIAMS NIH HHS
ID : R01 AR071491
Pays : United States
Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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