Session Information
Date: Sunday, November 8, 2015
Session Title: Genetics, Genomics and Proteomics Poster I
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose:
Group of monogenic autoinflammatory syndromes is characterized by recurrent episodes of fever and inflammation.
Methods:
The study included 90 pts (37 boys, 63 girls) at the age from 1 to 17 y. (8.2 (4.7; 11.5) followed with a diagnosis of systemic JIA. The median age of disease onset was 3.0 (1.5; 5.1) y., disease duration – 4.4 (1.0; 7.6)y.
The commonest features were fever (100%), arthritis or arthragia (100%), rash (96%), hepato- and splenomegaly (96%), lymphadenopathy (94%), headache (62%), abdominal pain (58%), eye manifestations (21%). The patients were selected according to the clinical manifestations, with subsequent obligatory genetic counseling in the Department of Rheumatology of the Scientific Center for Children’s Health. Pts’ DNA was sequenced in all coding exons and intronic flanks of the TNFRSF1A and NLRP3 genes whose mutations cause autoinflammatory syndromes, TRAPS and CAPS, respectively.
Results:
In 13/90 (14.4%) pts genetic autoinflammatory syndrome was established. In 10/13 pts, we found mutations in TNFRSF1A: in 8/10 pts – the most frequent mutations c.362G>A (p.R92Q) located in exon 4 and associated with the mild progression of TRAPS. One TRAPS pt. had a frameshift mutation с.792delT (p.Lys265Serfs*87) in exon 9 of TNFRSF1A gene. Another pt. revealed a TNFRSF1A mutation known c.374G>A (C96Y).
The median age of disease onset was 5.1 years. A family history was present in 3 patients: 2 girls with R92Q variant and 1 – with C96Y mutation. 3 pts with symptomes of CAPS identified mutations in NLRP3 gene. None of the mutations were previously described in the databases for mutations. One pt. with a clinical picture of the CINCA, had a mutation c.796C>T (p.Leu266Phe) in exon 04 of NLRP3 gene. 2 other pts had mutations c.2861C>T and c.2173C>A, respectively. Pts with c.2173C>A mutation has CINCA/NOMID phenotype and dramatic effect of canacinumab. In 7 (7.5%) pts we identified NLRP3 gene polymorphism c.2113C>A, associated with elevated levels of IL1.
Conclusion:
Our results suggests for a relatively frequent incidence of CAPS and TRAPS in Russian systemic JIA patients. The number of genetically confirmed patients with periodic fever syndromes in Russia is very low. In order to identify more patients in the future, it is important to organize educational programs for increasing the knowledge on these diseases, to establish a network for genetic testing of periodic fever syndromes and to carry out differential diagnoses.
To cite this abstract in AMA style:
Alexeeva E, Baranov A, Savostyanov K, Pushkov A, Sleptsova T, Bzarova T, Valieva S, Denisova R, Isayeva K, Chistyakova E, Alexandra C. The Molecular Genetic Analysis of the Autoinflammatory Syndromes in Russian Patients with Manifestation of Systemic Juvenile Idiopathic Arthritis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-molecular-genetic-analysis-of-the-autoinflammatory-syndromes-in-russian-patients-with-manifestation-of-systemic-juvenile-idiopathic-arthritis/. Accessed September 23, 2020.« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-molecular-genetic-analysis-of-the-autoinflammatory-syndromes-in-russian-patients-with-manifestation-of-systemic-juvenile-idiopathic-arthritis/