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Analysis of NLRP3, MVK and TNFRSF1A variants in adult Greek patients with autoinflammatory symptoms
P. Karagianni1, A. Nezos2, F. Ioakeim3, A.G. Tzioufas4, H.M. Moutsopoulos5
- Department of Pathophysiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
- Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Greece.
- Department of Pathophysiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece.
- Department of Pathophysiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece. agtzi@med.uoa.gr
- Department of Pathophysiology, National and Kapodistrian University of Athens, Faculty of Medicine, Athens, Greece. hmoutsop@med.uoa.gr
CER11413
2018 Vol.36, N°6 ,Suppl.115
PI 0086, PF 0089
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PMID: 30418111 [PubMed]
Received: 21/05/2018
Accepted : 28/08/2018
In Press: 09/11/2018
Published: 13/12/2018
Abstract
OBJECTIVES:
Autoinflammatory diseases are characterised by abnormal hyperactivity of the innate immune system, causing systemic inflammation. The cryopyrin associated periodic syndrome (CAPS), the hyper IgD syndrome (HIDS) and the TNF receptor-associated periodic syndrome (TRAPS), are autoinflammatory conditions associated with mutations in the NLRP3, MVK and TNFRSF1A genes, respectively. We present the experience of our Department with these rare syndromes analysing genetic and clinical data of adult patients encountered between January 2011 and September 2017.
METHODS:
Eighty-eight adult patients with clinical suspicion of CAPS, HIDS and TRAPS were sequentially recruited and genetically tested for specific mutations in NLRP3, MVK and TNFRSF1A using Sanger sequencing. Clinical picture of mutation carriers was reviewed. Allele frequencies were compared to those described for the normal population by the 1000 Genomes project.
RESULTS:
Seventy-two of the 88 adult patients were found to be positive for mutations or polymorphisms. One patient carried two pathogenic MVK mutations (pV377I/c.1129G>A and c.850delG) and another one carried a pathogenic heterozygous pΑ439V/c.1316C>T NLRP3 mutation. Seventeen patients carried variants of uncertain significance. The pS434S/c.1302C>T NLRP3 mutation is slightly increased in our patients compared to the reference population and seems to correlate with severe symptom presentation.
CONCLUSIONS:
In rare cases, periodic fever and inflammatory symptoms in adults can be attributed to mutations in NLRP3, MVK and TNFRSF1A. Clinical assessment and genetic analysis are critical for proper diagnosis and treatment of autoinflammatory diseases.
