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Pediatric Rheumatology
Published in: Pediatric Rheumatology 1/2015

Open Access 01-12-2015 | Research article

Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study

Authors: Carlo De Pieri, Josef Vuch, Eleonora De Martino, Anna M Bianco, Luca Ronfani, Emmanouil Athanasakis, Barbara Bortot, Sergio Crovella, Andrea Taddio, Giovanni M Severini, Alberto Tommasini

Published in: Pediatric Rheumatology | Issue 1/2015

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Abstract

Background

Periodic fever syndromes (PFS) are an emerging group of autoinflammatory disorders. Clinical overlap exists and multiple genetic analyses may be needed to assist diagnosis. We evaluated the diagnostic value of a 5-gene sequencing panel (5GP) in patients with undiagnosed PFS.

Methods

Simultaneous double strand Sanger sequencing of MEFV, MVK, TNFRSF1A, NLRP3, NLRP12 genes was performed in 42 patients with unexplained PFS. Clinical features were correlated with genetic results.

Results

None of 42 patients analyzed displayed a causative genotype. However, single or multiple genetic variants of uncertain significance were detected in 24 subjects. Only in 5 subjects a definite diagnosis was made by taking into account both genetic and clinical data (2 TRAPS syndrome; 2 FMF; 1 FCAS). Statistical analysis showed that patients carrying genetic variants in one or more of the five selected genes displayed a significantly lower response to glucocorticoids compared with subjects who had completely negative genetic results.

Conclusions

The sequencing of multiple genes is of little help in the diagnostics of PFS and can often lead to results of uncertain interpretation, thus the clinically driven sequencing of single genes should remain the recommended approach. However, the presence of single or multiple genetic variants of uncertain significance, even if not allowing any specific diagnosis, correlated with a poorer response to glucocorticoids, possibly indicating a multifactorial subgroup of PFS with differential response to pharmacological treatment.
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Metadata
Title
Genetic profiling of autoinflammatory disorders in patients with periodic fever: a prospective study
Authors
Carlo De Pieri
Josef Vuch
Eleonora De Martino
Anna M Bianco
Luca Ronfani
Emmanouil Athanasakis
Barbara Bortot
Sergio Crovella
Andrea Taddio
Giovanni M Severini
Alberto Tommasini
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Pediatric Rheumatology / Issue 1/2015
Electronic ISSN: 1546-0096
DOI
https://doi.org/10.1186/s12969-015-0006-z

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