Familial Chilblain Lupus Due to a Novel Mutation in the Exonuclease III Domain of 3′ Repair Exonuclease 1 (TREX1)
Research output: Contribution to journal › Case report › Contributed › peer-review
Contributors
Abstract
IMPORTANCE: Familial chilblain lupus is a rare, autosomal dominant form of lupus erythematosus characterized by cold-induced inflammatory lesions at acral locations presenting in early childhood. Familial chilblain lupus is usually caused by a mutation in TREX1 (3' repair exonuclease 1). OBSERVATIONS: We report on a family with dominant chilblain lupus segregating a novel TREX1 mutation (c.585C>G; H195Q) within the highly conserved exonuclease (Exo) III domain. Affected family members experienced cold-induced chilblain lesions of varying degrees, ranging from bluish-red infiltrations to mutilating necrotic ulcerations. In addition, all patients showed signs of systemic disease, such as arthritis, lymphopenia, or antinuclear antibodies. An increased expression of myxovirus resistance protein A in the skin and induction of interferon-stimulated genes in peripheral blood cells demonstrated activation of type I interferon. CONCLUSIONS AND RELEVANCE: This case further implicates type I interferon-dependent innate immune activation in the pathogenesis of TREX1-associated familial chilblain lupus. Unlike previously reported TREX1 mutations, which affect the Exo I or Exo II domains, the mutation presented here alters the Exo III domain, suggesting a particular role of mutations within the catalytic Exo domains in the pathogenesis of familial chilblain lupus. The high prevalence of extracutaneous manifestations, along with activation of type I interferon, underlines the systemic nature of familial chilblain lupus.
Details
Original language | English |
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Pages (from-to) | 426-431 |
Number of pages | 6 |
Journal | JAMA Dermatology |
Volume | 151 |
Issue number | 4 |
Publication status | Published - 1 Apr 2015 |
Peer-reviewed | Yes |
External IDs
researchoutputwizard | legacy.publication#66051 |
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Scopus | 84928252776 |
PubMed | 25517357 |
ORCID | /0000-0002-4330-1861/work/148606012 |