التفاصيل البيبلوغرافية
| العنوان: |
Whole genome sequencing identifies novel genetic mutations in patients with eczema herpeticum |
| المؤلفون: |
Bin, Lianghua, Malley, Claire, Taylor, Patricia, Boorgula, Meher Preethi, Chavan, Sameer, Daya, Michelle, Mathias, Malaika, Shankar, Gautam, Rafaels, Nicholas, Vergara, Candelaria, Potee, Joseph, Campbell, Monica, Hanifin, Jon M, Simpson, Eric, Schneider, Lynda C, Gallo, Richard L, Hata, Tissa, Paller, Amy S, De Benedetto, Anna, Beck, Lisa A, Ong, Peck Y, Guttman‐Yassky, Emma, Richers, Brittany, Baraghoshi, David, Ruczinski, Ingo, Barnes, Kathleen C, Leung, Donald YM, Mathias, Rasika A |
| المصدر: |
Allergy, vol 76, iss 8 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2021 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Biotechnology, Sexually Transmitted Infections, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Skin, Dermatitis, Atopic, Glutathione Transferase, Herpesvirus 1, Human, Humans, Kaposi Varicelliform Eruption, Mutation, Nucleotide Transport Proteins, Whole Genome Sequencing, atopic dermatitis, eczema herpeticum, herpes simplex virus, SIDT2, Immunology, Allergy |
| الوقت: |
2510 - 2523 |
| الوصف: |
BackgroundEczema 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+).MethodsWhole 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.ResultsEight 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).ConclusionSIDT2 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. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt3sk7j3fn; https://escholarship.org/uc/item/3sk7j3fnTest |
| الإتاحة: |
https://escholarship.org/uc/item/3sk7j3fnTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.6E1DAF14 |
| قاعدة البيانات: |
BASE |
