Molekulargenetisches Labor
Zentrum für Nephrologie und Stoffwechsel
Moldiag Erkrankungen Gene Support Kontakt

Pyrin

Das MEVF-Gen kodiert einen wichtiges Steuerungsprotein der angeborenen Immunität. Das Protein ist auch als Pyrin oder Marenostrin bekannt. Die Erkrankungen werden als Pyrin-assoziierte autoinflammatorische Erkrankungen zusammengefasst. Die Vererbung ist entweder dominant oder rezessiv.

Interpretation

Die durch Mutationen im MEFV-Gen hervorgerufenen Erkrankungen werden als Pyrin-assoziierte autoinflammatorische Erkrankungen. Das rezessive familiäre Mittelmeerfieber wird vor allem durch Mutationen im Exon 10, welches die Pyrin B30.2-Domäne kodiert, ausgelöst. Es sind auch auch eine ganze Reihe von Patienten mit nur einer Mutation in diesem Exon als dominante Erkrankung beschrieben. Zu einem Teil lässt sich dieser schwerere Verlauf auch durch zusätzliche Mutationen in den Exons 3 (p.Pro373Leu), Exon 5 (p.His478Tyr) oder Exon 8 (p.Thr577/Ser/Asn/Ala) erklären.

Ein anderer Phänotyp, die dominante Pyrin-assoziierte Autoinflammation mit neutrophiler Dermatosis wird insbesondere durch Missense-Mutationen der Codons 242 und 244 im Exon 2 ausgelöst. Diese Veränderungen beeinflussen die von der Phosophorilierung abhängige endogene Inhibition durch das 14-3-3-Protein.

Gentests:

Klinisch Untersuchungsmethoden Familienuntersuchung
Bearbeitungszeit 5 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Hochdurchsatz-Sequenzierung
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Direkte Sequenzierung der proteinkodierenden Bereiche eines Gens
Bearbeitungszeit 25 Tage
Probentyp genomische DNS
Klinisch Untersuchungsmethoden Multiplex ligationsabhängige Amplifikation
Bearbeitungszeit 25 Tage
Probentyp genomische DNS

Verknüpfte Erkrankungen:

Familiäres Mittelmeerfieber
MEFV
SAA1
TNFRSF1A

Referenzen:

1.

Aldea A et al. (2004) A severe autosomal-dominant periodic inflammatory disorder with renal AA amyloidosis and colchicine resistance associated to the MEFV H478Y variant in a Spanish kindred: an unusual familial Mediterranean fever phenotype or another MEFV-associated periodic inflammatory disorder?

external link
2.

Yilmaz E et al. (2001) Mutation frequency of Familial Mediterranean Fever and evidence for a high carrier rate in the Turkish population.

external link
3.

Kogan A et al. (2001) Common MEFV mutations among Jewish ethnic groups in Israel: high frequency of carrier and phenotype III states and absence of a perceptible biological advantage for the carrier state.

external link
4.

Gershoni-Baruch R et al. (2001) Familial Mediterranean fever: prevalence, penetrance and genetic drift.

external link
5.

Medlej-Hashim M et al. (2001) Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations.

external link
6.

Medlej-Hashim M et al. (2002) Familial Mediterranean fever: the potential for misdiagnosis of E148V using the E148Q usual RFLP detection method.

external link
7.

Gershoni-Baruch R et al. (2002) The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever.

external link
8.

Gershoni-Baruch R et al. (2002) Familial Mediterranean fever: the segregation of four different mutations in 13 individuals from one inbred family: genotype-phenotype correlation and intrafamilial variability.

external link
9.

Chae JJ et al. (2003) Targeted disruption of pyrin, the FMF protein, causes heightened sensitivity to endotoxin and a defect in macrophage apoptosis.

external link
10.

Gershoni-Baruch R et al. (2003) The contribution of genotypes at the MEFV and SAA1 loci to amyloidosis and disease severity in patients with familial Mediterranean fever.

external link
11.

None (2001) Modifier genes in mice and humans.

external link
12.

Chae JJ et al. (2006) The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production.

external link
13.

Jalkh N et al. (2008) Familial Mediterranean Fever in Lebanon: founder effects for different MEFV mutations.

external link
14.

Fragouli E et al. (2008) Familial Mediterranean Fever in Crete: a genetic and structural biological approach in a population of 'intermediate risk'.

external link
15.

Grandemange S et al. (2009) Expression of the familial Mediterranean fever gene is regulated by nonsense-mediated decay.

external link
16.

Bathelier C et al. (2010) Screening for the M694V mutation of the familial Mediterranean fever (FMF) gene in 604 French patients.

external link
17.

Chen X et al. (1998) Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF).

external link
18.

Bernot A et al. (1998) Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF).

external link
19.

Dewalle M et al. (1998) Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF).

external link
20.

Touitou I et al. (2004) Infevers: an evolving mutation database for auto-inflammatory syndromes.

external link
21.

Livneh A et al. (2001) A single mutated MEFV allele in Israeli patients suffering from familial Mediterranean fever and Behçet's disease (FMF-BD).

external link
22.

Cazeneuve C et al. (2000) Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever.

external link
23.

Shoham NG et al. (2003) Pyrin binds the PSTPIP1/CD2BP1 protein, defining familial Mediterranean fever and PAPA syndrome as disorders in the same pathway.

external link
24.

Yu JW et al. (2007) Pyrin activates the ASC pyroptosome in response to engagement by autoinflammatory PSTPIP1 mutants.

external link
25.

Aksentijevich I et al. (1999) Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.

external link
26.

Mansfield E et al. (2001) The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments.

external link
27.

El-Shanti H et al. (2006) Familial mediterranean fever in Arabs.

external link
28.

Bonyadi M et al. (2009) MEFV mutations in Iranian Azeri Turkish patients with familial Mediterranean fever.

external link
29.

Yuval Y et al. (1995) Dominant inheritance in two families with familial Mediterranean fever (FMF).

external link
30.

None (1997) A candidate gene for familial Mediterranean fever.

external link
31.

None (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium.

external link
32.

Babior BM et al. (1997) The familial Mediterranean fever gene--cloned at last.

external link
33.

Booth DR et al. (1998) SAA1 alleles as risk factors in reactive systemic AA amyloidosis.

external link
34.

Cazeneuve C et al. (1999) MEFV-Gene analysis in armenian patients with Familial Mediterranean fever: diagnostic value and unfavorable renal prognosis of the M694V homozygous genotype-genetic and therapeutic implications.

external link
35.

Centola M et al. (2000) The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators.

external link
36.

Chae JJ et al. (2000) Isolation, genomic organization, and expression analysis of the mouse and rat homologs of MEFV, the gene for familial mediterranean fever.

external link
37.

Papin S et al. (2000) Alternative splicing at the MEFV locus involved in familial Mediterranean fever regulates translocation of the marenostrin/pyrin protein to the nucleus.

external link
38.

Mansour I et al. (2001) Familial Mediterranean fever in Lebanon: mutation spectrum, evidence for cases in Maronites, Greek orthodoxes, Greek catholics, Syriacs and Chiites and for an association between amyloidosis and M694V and M694I mutations.

external link
39.

Schaner P et al. (2001) Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states.

external link
40.

None (2001) The spectrum of Familial Mediterranean Fever (FMF) mutations.

external link
41.

NCBI article

NCBI 4210 external link
42.

OMIM.ORG article

Omim 608107 external link
43.

Orphanet article

Orphanet ID 123191 external link
Update: 14. August 2020
Copyright © 2005-2024 Zentrum für Nephrologie und Stoffwechsel, Dr. Mato Nagel
Albert-Schweitzer-Ring 32, D-02943 Weißwasser, Deutschland, Tel.: +49-3576-287922, Fax: +49-3576-287944
Seitenüberblick | Webmail | Haftungsausschluss | Datenschutz | Impressum