The Pyrin Family of Fever Genes

Shinkai, Kanade; Kilcline, Christine; Connolly, M. Kari; Frieden, Ilona J.

doi:10.1001/archderm.141.2.242

Cited by 30 publications

(2 citation statements)

References 60 publications

(94 reference statements)

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“…[2][3][4][7][8][9] FMF is the result of a mutation in the gene MEFV which codes for pyrin, a protein that helps regulate molecular signaling pathways involved in inflammation, cytokine and chemokine processing, and apoptosis. 10 To our knowledge, the pyrin genes of Shar Pei dogs have not been investigated.…”

Section: Discussionmentioning

confidence: 99%

Liver aspirate from a Shar Pei dog

Flatland¹,

Moore²,

Wolf³

et al. 2007

Veterinary Clinical Pathol

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A 5-year-old, neutered male, Shar Pei dog was presented with weight loss, anorexia, lethargy, stranguria, and distal limb edema. Clinicopathologic abnormalities included anemia, an inflammatory leukogram, azotemia, icterus, urinary tract infection, and hepatomegaly with a markedly hypoechoic liver. Cytologic findings in a fine-needle aspirate of the liver included large amounts of amorphous, pink, extracellular matrix between hepatocytes. The amorphous material was congophilic using Congo red stain on a hepatic cytology specimen and green birefringent areas were observed under polarized light, confirming the presence of amyloid. The dog was euthanized and a necropsy was done. Histopathologic evaluation using H&E and Congo red staining confirmed amyloid deposits within the liver, kidneys, intestinal vessels, pancreas, and mesenteric ganglia. Immunohistochemical staining of liver and kidney sections using anti-AA amyloid and anti-P component antibodies confirmed the presence of AA amyloid. In this case, we demonstrated that Congo red staining and polarized light microscopy are a useful diagnostic technique in cytologic specimens of suitable thickness for confirming the presence of amyloid.

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Section: Discussionmentioning

confidence: 99%

Liver aspirate from a Shar Pei dog

Flatland¹,

Moore²,

Wolf³

et al. 2007

Veterinary Clinical Pathol

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“…The NLR (nucleotide binding domain and leucine rich, or NOD-like receptor, where NOD is an abbreviation for nucleotide oligomerization domain) family of genes also contain the PYD domain [27], [28], [29], [30]. While the pyrin protein is thought to function in apoptotic and inflammatory signaling pathways [31], [32], its exact function has been debated. In a better-studied system, cryopyrin or NLRP3, which also has the PYD domain, is activated to assemble the inflammasome [33], a multi-protein structure that ultimately results in activation of pro-caspase-1 that, in turn, processes pro-IL-1β to IL-1β.…”

Section: Introductionmentioning

confidence: 99%

Missense Mutations in the MEFV Gene Are Associated with Fibromyalgia Syndrome and Correlate with Elevated IL-1β Plasma Levels

Feng

Zhang

et al. 2009

PLoS ONE

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BackgroundFibromyalgia syndrome (FMS), a common, chronic, widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, has both genetic and environmental contributions. Patients and their parents have high plasma levels of the chemokines MCP-1 and eotaxin, providing evidence for both a genetic and an immunological/inflammatory origin for the syndrome (Zhang et al., 2008, Exp. Biol. Med. 233: 1171–1180).Methods and FindingsIn a search for a candidate gene affecting inflammatory pathways, among five screened in our patient samples (100 probands with FMS and their parents), we found 10 rare and one common alleles for MEFV, a gene in which various compound heterozygous mutations lead to Familial Mediterranean Fever (FMF). A total of 2.63 megabases of genomic sequence of the MEFV gene were scanned by direct sequencing. The collection of rare missense mutations (all heterozygotes and tested in the aggregate) had a significant elevated frequency of transmission to affecteds (p = 0.0085, one-sided, exact binomial test). Our data provide evidence that rare missense variants of the MEFV gene are, collectively, associated with risk of FMS and are present in a subset of 15% of FMS patients. This subset had, on average, high levels of plasma IL-1β (p = 0.019) compared to FMS patients without rare variants, unaffected family members with or without rare variants, and unrelated controls of unknown genotype. IL-1β is a cytokine associated with the function of the MEFV gene and thought to be responsible for its symptoms of fever and muscle aches.ConclusionsSince misregulation of IL-1β expression has been predicted for patients with mutations in the MEFV gene, we conclude that patients heterozygous for rare missense variants of this gene may be predisposed to FMS, possibly triggered by environmental factors.

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