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Periodic fever syndromes: beyond the single gene paradigm Westwell-Roper, Clara; Niemietz, Iwona; Tucker, Lori B.; Brown, Kelly L.

Abstract

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease in Canada and is characterized by a clinical syndrome of episodic inflammatory symptoms. Traditionally, the disease is defined by autosomal recessive inheritance of MEFV gene variants, yet FMF also not uncommonly manifests in individuals with only one identified disease-associated allele. Increasing availability and affordability of gene sequencing has led to the identification of multiple MEFV variants; however, they are often of unknown clinical significance. Variants in other genes affecting overlapping or distinct inflammatory signaling pathways – together with gene-environment interactions including epigenetic modulation – likely underlie the significant genetic and phenotypic heterogeneity seen among patients with this disease. We review recent evidence of the expanding spectrum of FMF genotype and phenotype and suggest that current drug funding schemes restricting biologic agents to patients with homozygous mutations have not kept pace with our biological understanding of the disease.

Item Metadata

Title
Periodic fever syndromes: beyond the single gene paradigm
Creator
Westwell-Roper, Clara; Niemietz, Iwona; Tucker, Lori B.; Brown, Kelly L.
Contributor
Children's Hospital (Vancouver, B.C.); Children's Hospital (Vancouver, B.C.). Research Institute
Publisher
BioMed Central
Date Issued
2019-05-14
Description
Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease in Canada and is characterized by a clinical syndrome of episodic inflammatory symptoms. Traditionally, the disease is defined by autosomal recessive inheritance of MEFV gene variants, yet FMF also not uncommonly manifests in individuals with only one identified disease-associated allele. Increasing availability and affordability of gene sequencing has led to the identification of multiple MEFV variants; however, they are often of unknown clinical significance. Variants in other genes affecting overlapping or distinct inflammatory signaling pathways – together with gene-environment interactions including epigenetic modulation – likely underlie the significant genetic and phenotypic heterogeneity seen among patients with this disease. We review recent evidence of the expanding spectrum of FMF genotype and phenotype and suggest that current drug funding schemes restricting biologic agents to patients with homozygous mutations have not kept pace with our biological understanding of the disease.
Subject
Hereditary autoinflammatory diseases; Familial Mediterranean fever; Biological therapy; Interleukin-1; Pyrin; Genetic association studies
Genre
Article
Type
Text
Language
eng
Date Available
2019-05-22
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0378926
URI
http://hdl.handle.net/2429/70267
Affiliation
Medicine, Faculty of; Science, Faculty of; Medicine, Department of; Microbiology and Immunology, Department of
Citation
Pediatric Rheumatology. 2019 May 14;17(1):22
Publisher DOI
10.1186/s12969-019-0324-7
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)