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Cited by 33Dermatology and Skin DiseasesHerpesvirus Infections and TreatmentsGenetic and rare skin diseases.

Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum

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Bin, Lianghua, Malley, Claire, Taylor, Patricia, Preethi Boorgula, Meher, Chavan, Sameer, Daya, Michelle, Mathias, Malaika, Shankar, Gautam +20 more·2021·Allergy
DOI 10.1111/all.14762PMC PMC8978872
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Abstract

Background: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+). Methods: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH−) and 237 non‐atopic control (NA) subjects. Variants were annotated, and a gene‐based approach (SKAT‐O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation. Results: Eight genes were identified in the comparison of recurrent ADEH+to ADEH−and NA subjects: SIDT2, CLEC7A, GSTZ1, TPSG1, SP110, RBBP8NL, TRIM15, and FRMD3. Silencing SIDT2 and RBBP8NL in normal human primary keratinocytes (NHPKs) led to significantly increased HSV‐1 replication. SIDT2‐silenced NHPKs had decreased gene expression of IFNk and IL1b in response to HSV‐1 infection. RBBP8NL‐silenced NHPKs had decreased gene expression of IFNk, but increased IL1b. Additionally, silencing SIDT2 and RBBP8NL also inhibited gene expression of keratinocyte differentiation markers keratin 10 (KRT10) and loricrin (LOR). Conclusion: SIDT2 and RBBP8NL participate in keratinocyte's response to HSV‐1 infection. SIDT2 and RBBP8NL also regulate expression of keratinocyte differentiation genes of KRT10 and LOR.

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  • Whole-genome studies have also identified genes associated with AD complication phenotypes, such as eczema herpeticum, for example SIDT2 and RBBP8NL, which participate in the keratinocyte response to herpes virus type 1 infection.

    “Whole-genome studies have also identified genes associated with AD complication phenotypes, such as eczema herpeticum, for example SIDT2 and RBBP8NL, which participate in the keratinocyte response to herpes virus type 1 infection.”

    From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [39]

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Authors
Bin, L., Malley, C., Taylor, P., Preethi Boorgula, M., Chavan, S., Daya, M., Mathias, M., Shankar, G., Rafaels, N., Vergara, C., Potee, J., Campbell, M., Hanifin, J. M., Simpson, E., Schneider, L. C., Gallo, R. L., Hata, T., Paller, A. S., De Benedetto, A., Beck, L. A., Ong, P. Y., Guttman‐Yassky, E., Richers, B., Baraghoshi, D., Ruczinski, I., Barnes, K. C., Leung, D. Y. M., & Mathias, R. A.
Affiliations
  • National Jewish Health (US)
  • Johns Hopkins University (US)
  • Department of Medicine University of Colorado Aurora CO USA
  • University of Colorado Anschutz (US)
  • Precision for Medicine (United States) (US)
  • Oregon Health & Science University (US)
  • Boston Children's Hospital (US)
  • University of California San Diego (US)
  • Northwestern University (US)
  • University of Rochester Medical Center Rochester NY USA
  • University of Rochester Medicine (US)
  • University of Southern California (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
  • Leung, Donald Y. M.
  • Mathias, Rasika A.
ORCID
Venue
Allergy
Publisher
Wiley
Published
2021-03-15
Volume
76
Issue
8
Pages
2510-2523
ISSN
  • 0105-4538 (ISSN-L)
  • 1398-9995
DOI
10.1111/all.14762
PMC
PMC8978872
OpenAlex
W3129093686
Cited by
33
References
5
Citations by year
2026: 3 · 2025: 5 · 2024: 8 · 2023: 9 · 2022: 6 · 2021: 2
FWCI
5.56
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Allergy (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (1U19AI117673‐01, 1UM1AI151958)
  • National Center for Advancing Translational Sciences (UL1 TR000154)
  • National Center for Research Resources (UL1 RR025780)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and rare skin diseases.
Keywords
eczema herpeticum, atopic dermatitis, herpes simplex virus type 1, genetic susceptibility, SIDT2, keratinocyte differentiation, interferon-kappa, IL-1β, keratin 10, loricrin, HSV-1 replication, rare variants
MeSH terms
Whole Genome Sequencing, Dermatitis, Atopic, Glutathione Transferase, Humans, Kaposi Varicelliform Eruption, Mutation, Herpesvirus 1, Human, Nucleotide Transport Proteins

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