A novel TRAF3IP2 variant causing familial scarring alopecia with mixed features of discoid lupus erythematosus and folliculitis decalvans.
Adaptor Proteins, Signal Transducing
/ genetics
Adolescent
Alopecia
/ diagnostic imaging
Child
Child, Preschool
Consanguinity
Female
Folliculitis
/ diagnostic imaging
Genetic Predisposition to Disease
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Lupus Erythematosus, Discoid
/ diagnostic imaging
Male
Pedigree
Protein Binding
/ genetics
Protein Interaction Maps
Receptors, Interleukin-17
/ genetics
Sequence Analysis, RNA
Exome Sequencing
TRAF3IP2
alopecia
lupus
scarring
skin
Journal
Clinical genetics
ISSN: 1399-0004
Titre abrégé: Clin Genet
Pays: Denmark
ID NLM: 0253664
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
15
03
2020
revised:
21
04
2020
accepted:
22
04
2020
pubmed:
1
5
2020
medline:
10
7
2021
entrez:
1
5
2020
Statut:
ppublish
Résumé
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.
Substances chimiques
Adaptor Proteins, Signal Transducing
0
IL17RA protein, human
0
Intracellular Signaling Peptides and Proteins
0
Receptors, Interleukin-17
0
TRAF3IP2 protein, human
0
Tifab protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
116-125Informations de copyright
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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