A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.
Georges NemerNehme El-HachemEdward Said EidLamiaa HamieTara BardawilSamar KhalilInaam El-RassyRemi SafiAthar KhalilOssama AbbasYutaka ShimomuraMazen KurbanPublished in: Clinical genetics (2020)
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.
Keyphrases
- genome wide
- single cell
- copy number
- systemic lupus erythematosus
- dna methylation
- disease activity
- mental health
- binding protein
- intellectual disability
- induced apoptosis
- rheumatoid arthritis
- healthcare
- oxidative stress
- poor prognosis
- physical activity
- amino acid
- multiple sclerosis
- gene expression
- photodynamic therapy
- protein protein
- emergency department
- early onset
- single molecule
- signaling pathway
- idiopathic pulmonary fibrosis
- endoplasmic reticulum stress
- cell death
- drug induced
- cell proliferation