Familial Chilblain Lupus Due to a Novel Mutation in the Exonuclease III Domain of 3′ Repair Exonuclease 1 (TREX1)

• Autores: Claudia Günther, Nicole Berndt, Christine Wolf, Min Ae Lee-Kirsch
• Localización: JAMA Dermatology, ISSN 2168-6068, Vol. 151, Nº. 4, 2015, págs. 426-431
• Idioma: inglés
• Texto completo no disponible (Saber más ...)
• Resumen

  • 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