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A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans
Author(s) -
Nemer Georges,
ElHachem Nehme,
Eid Edward,
Hamie Lamiaa,
Bardawil Tara,
Khalil Samar,
ElRassy Inaam,
Safi Remi,
Khalil Athar,
Abbas Ossama,
Shimomura Yutaka,
Kurban Mazen
Publication year - 2020
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13767
Subject(s) - discoid lupus erythematosus , missense mutation , biology , exome sequencing , scarring alopecia , hair loss , exome , folliculitis , genetics , transcriptome , immunology , gene , lupus erythematosus , mutation , scalp , gene expression , antibody , anatomy
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.