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Title:
Evidence for genetic overlap between adult onset Stillâs disease and hereditary periodic fever syndromes | Rheumatology International
Description:
Objective Adult onset Stillâs 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. Methods 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 (nâ=â6) 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. Results We identified three rare variants in MEFV, one previously not described. Association to the three likely pathogenic MEFV variants was significant (p câ=â2.34Eââ03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p câ=â2.40Eââ04), as 5% of patients (2/40) carried a (likely) pathogenic variant in this gene. Both of them received a biological for treatment. Conclusion 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.
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Keywords {đ}
pubmed, article, google, scholar, cas, disease, stills, patients, central, fever, mutations, syndrome, rheumatol, periodic, clinical, variants, gene, adultonset, adult, syndromes, mefv, familial, arthritis, genetic, study, mediterranean, res, onset, hereditary, aosd, autoinflammatory, tnfrsfa, pyrin, tumour, necrosis, clin, genet, privacy, cookies, content, analysis, data, research, rheumatology, evidence, nlrp, pathogenic, association, access, factor,
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Questions {â}
- Mehta B, Efthimiou P (2012) Ferritin in adult-onset Stillâs disease: just a useful innocent bystander?
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headline:Evidence for genetic overlap between adult onset Stillâs disease and hereditary periodic fever syndromes
description:Adult onset Stillâs 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 (nâ=â6) 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
câ=â2.34Eââ03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p
câ=â2.40Eââ04), 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.
datePublished:2017-11-20T00:00:00Z
dateModified:2017-11-20T00:00:00Z
pageStart:111
pageEnd:120
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Adult onset Stillâs disease
Biological therapy
Familial Mediterranean fever
Hereditary periodic fever syndromes
TNF receptor-associated periodic syndrome
Autoinflammatory syndromes
Rheumatology
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headline:Evidence for genetic overlap between adult onset Stillâs disease and hereditary periodic fever syndromes
description:Adult onset Stillâs 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 (nâ=â6) 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
câ=â2.34Eââ03), and two of the three carriers had a severe course of disease. We observed strong evidence for significant association to mutations in TNFRSF1A (p
câ=â2.40Eââ04), 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.
datePublished:2017-11-20T00:00:00Z
dateModified:2017-11-20T00:00:00Z
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Adult onset Stillâs disease
Biological therapy
Familial Mediterranean fever
Hereditary periodic fever syndromes
TNF receptor-associated periodic syndrome
Autoinflammatory syndromes
Rheumatology
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