Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes

Sighart R, Rech J, Hueber A, Blank N, Löhr S, Reis A, Sticht H, Hüffmeier U (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Rheumatology International Springer Verlag (Germany)

Abstract

Adult onset Still's disease (AOSD) is a severe, autoimmune disease that can be challenging to treat with conventional therapeutics and biologicals in a considerable number of cases. Therefore, there is a high need to understand its pathogenesis better. As major clinical symptoms overlap between AOSD and hereditary periodic fever syndromes (HPFS), we analysed four known HPFS genes in AOSD.We performed Sanger sequencing and quantitative analysis of all coding regions of MEFV, TNFRSF1A, MVK and NLRP3 in 40 AOSD patients. All rare coding variants (n = 6) were evaluated for several aspects to classify them as benign to pathogenic variants. Statistical analysis was performed to analyse whether variants classified as (likely) pathogenic were associated with AOSD.We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p c = 2.34E- 03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p c = 2.40E- 04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment.Our results indicate TNFRSF1A as a relevant gene in AOSD, especially in patients with a more challenging course of disease, while causal variants remain to be identified in the majority of patients.

Authors with CRIS profile

Regina Sighart Medizinische Fakultät Axel Hueber Department of Medicine 3 – Rheumatology and Immunology André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Heinrich Sticht Professur für Bioinformatik Ulrike Hüffmeier Lehrstuhl für Humangenetik

Involved external institutions

Ruprecht-Karls-Universität Heidelberg

Germany (DE)

How to cite

APA:

Sighart, R., Rech, J., Hueber, A., Blank, N., Löhr, S., Reis, A.,... Hüffmeier, U. (2017). Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes. Rheumatology International. https://dx.doi.org/10.1007/s00296-017-3885-0

MLA:

Sighart, Regina, et al. "Evidence for genetic overlap between adult onset Still's disease and hereditary periodic fever syndromes." Rheumatology International (2017).

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