- Oral presentation
- Open Access
- Published:
Familial chilblain lupus caused by an activating mutation in STING
Pediatric Rheumatology volume 13, Article number: O62 (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.
Author information
Authors and Affiliations
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.
The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
König, N., Fiehn, C., Lorenz, HM. et al. Familial chilblain lupus caused by an activating mutation in STING. Pediatr Rheumatol 13 (Suppl 1), O62 (2015). https://doi.org/10.1186/1546-0096-13-S1-O62
Published:
DOI: https://doi.org/10.1186/1546-0096-13-S1-O62
Keywords
- Lung Disease
- Interstitial Lung Disease
- Exome Sequencing
- Necrotizing Lesion
- Cutaneous Lesion