Volume 13 Supplement 1

8th International Congress of Familial Mediterranean Fever and Systemic Autoinflammatory Diseases

Open Access

Familial chilblain lupus caused by an activating mutation in STING

  • N König1,
  • C Fiehn2,
  • H-M Lorenz2, 3 and
  • MA Lee-Kirsch1
Pediatric Rheumatology201513(Suppl 1):O62

https://doi.org/10.1186/1546-0096-13-S1-O62

Published: 28 September 2015

Familial chilblain lupus is a monogenic form of cutaneous lupus erythematosus characterized by cold-induced cutaneous lesions at acral location. It is caused by loss-of-function mutations in the nucleic acid metabolizing enzymes TREX1 or SAMHD1. Gain-of-function mutations in STING (stimulator of Interferon genes) have been described in an infancy-onset autoinflammatory syndrome with fever, inflammatory cutaneous lesions and interstitial lung disease.

Here we report on a family with dominant chilblain lupus over 4 generations. Affected family members presented with acral inflammatory and partially necrotizing lesions beginning in early childhood. In some cases, low-titered ANAs and immune complexes were detectable. The family tested negative for TREX1 or SAMHD1 mutations. Exome sequencing revealed a heterozygous STING mutation segregating with chilblain lupus in the family. The mutation affects a highly conserved residue within the STING dimer interface and is predicted to be pathogenic. Quantitative RT-PCR analysis showed an increased expression of IFN-stimulated genes in blood cells of affected family members suggesting that the identified mutation has an activating effect on type I IFN signaling. Taken together, our findings demonstrate that gain-of-function mutations in STING can cause familial chilblain lupus and expand the spectrum of type I interferonopathies.

Authors’ Affiliations

(1)
Technische Universität Dresden, Molekulare Pädiatrie, Klinik für Kinder- und Jugendmedizin
(2)
ACURA-Rheumazentrum
(3)
Universität Heidelberg, Sektion Rheumatologie

Copyright

© König et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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