Tags

Type your tag names separated by a space and hit enter

A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.
Clin Genet. 2020 Aug; 98(2):116-125.CG

Abstract

Discoid lupus erythematosus (DLE) is an autoimmune disorder with a poorly defined etiology. Despite epidemiologic gender and ethnic biases, a clear genetic basis for DLE remains elusive. In this study, we used exome and RNA sequencing technologies to characterize a consanguineous Lebanese family with four affected individuals who presented with classical scalp DLE and generalized folliculitis. Our results unraveled a novel biallelic variant c.1313C > A leading to a missense substitution p.(Thr438Asn) in TRAF3IP2(NM_147200.3). Expression studies in cultured cells revealed mis-localization of the mutated protein. Functional characterization of the mutated protein showed significant reduction in the physical interaction with the interleukin 17-A receptor (IL17RA), while interaction with TRAF6 was unaffected. By conducting a differential genome-wide transcriptomics analysis between affected and non-affected individuals, we showed that the hair follicle differentiation pathway is drastically suppressed, whereas cytokine and inflammation responses are significantly upregulated. Furthermore, our results were highly concordant with molecular signatures in patients with DLE from a public dataset. In conclusion, this is the first report on a new putative role for TRAF3IP2 in the etiology of DLE. The identified molecular features associated with this gene could pave the way for better DLE-targeted treatment.

Authors+Show Affiliations

Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon. Pillar Genomics Institute of Precision Medicine, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Pillar Genomics Institute of Precision Medicine, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.Dermatology, American University of Beirut, Beirut, Lebanon.Department of Dermatology, Yamaguchi University, Yamaguchi, Japan.Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon. Dermatology, American University of Beirut, Beirut, Lebanon.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32350852

Citation

Nemer, Georges, et al. "A Novel TRAF3IP2 Variant Causing Familial Scarring Alopecia With Mixed Features of Discoid Lupus Erythematosus and Folliculitis Decalvans." Clinical Genetics, vol. 98, no. 2, 2020, pp. 116-125.
Nemer G, El-Hachem N, Eid E, et al. A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans. Clin Genet. 2020;98(2):116-125.
Nemer, G., El-Hachem, N., Eid, E., Hamie, L., Bardawil, T., Khalil, S., El-Rassy, I., Safi, R., Khalil, A., Abbas, O., Shimomura, Y., & Kurban, M. (2020). A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans. Clinical Genetics, 98(2), 116-125. https://doi.org/10.1111/cge.13767
Nemer G, et al. A Novel TRAF3IP2 Variant Causing Familial Scarring Alopecia With Mixed Features of Discoid Lupus Erythematosus and Folliculitis Decalvans. Clin Genet. 2020;98(2):116-125. PubMed PMID: 32350852.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans. AU - Nemer,Georges, AU - El-Hachem,Nehme, AU - Eid,Edward, AU - Hamie,Lamiaa, AU - Bardawil,Tara, AU - Khalil,Samar, AU - El-Rassy,Inaam, AU - Safi,Remi, AU - Khalil,Athar, AU - Abbas,Ossama, AU - Shimomura,Yutaka, AU - Kurban,Mazen, Y1 - 2020/06/29/ PY - 2020/03/15/received PY - 2020/04/21/revised PY - 2020/04/22/accepted PY - 2020/5/1/pubmed PY - 2020/5/1/medline PY - 2020/5/1/entrez KW - TRAF3IP2 KW - alopecia KW - lupus KW - scarring KW - skin SP - 116 EP - 125 JF - Clinical genetics JO - Clin. Genet. VL - 98 IS - 2 N2 - Discoid lupus erythematosus (DLE) is an autoimmune disorder with a poorly defined etiology. Despite epidemiologic gender and ethnic biases, a clear genetic basis for DLE remains elusive. In this study, we used exome and RNA sequencing technologies to characterize a consanguineous Lebanese family with four affected individuals who presented with classical scalp DLE and generalized folliculitis. Our results unraveled a novel biallelic variant c.1313C > A leading to a missense substitution p.(Thr438Asn) in TRAF3IP2(NM_147200.3). Expression studies in cultured cells revealed mis-localization of the mutated protein. Functional characterization of the mutated protein showed significant reduction in the physical interaction with the interleukin 17-A receptor (IL17RA), while interaction with TRAF6 was unaffected. By conducting a differential genome-wide transcriptomics analysis between affected and non-affected individuals, we showed that the hair follicle differentiation pathway is drastically suppressed, whereas cytokine and inflammation responses are significantly upregulated. Furthermore, our results were highly concordant with molecular signatures in patients with DLE from a public dataset. In conclusion, this is the first report on a new putative role for TRAF3IP2 in the etiology of DLE. The identified molecular features associated with this gene could pave the way for better DLE-targeted treatment. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/32350852/A_novel_TRAF3IP2_variant_causing_familial_scarring_alopecia_with_mixed_features_of_discoid_lupus_erythematosus_and_folliculitis_decalvans L2 - https://doi.org/10.1111/cge.13767 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.