Details of Disease

General Information of Disease (ID: DISVP5WP)

• Disease Name: Familial Mediterranean fever
• Synonyms: benign paroxysmal peritonitis; periodic disease; FMF; familial paroxysmal polyserositis; Fiebre mediterrnea familiar; benign recurrent polyserositis
• Definition: Familial Mediterranean fever (FMF) is an autoinflammatory disorder characterized by recurrent short episodes of fever and serositis resulting in pain in the abdomen, chest, joints and muscles.
• Disease Hierarchy:
  DISAEGPH: Immune system disorder
  DISS9RWQ: Hereditary periodic fever syndrome
  DISVP5WP: Familial Mediterranean fever
• Disease Identifiers:
  MONDO ID: MONDO_0018088
  MESH ID: D010505
  UMLS CUI: C0031069
  OMIM ID: 249100
  MedGen ID: 45811
  Orphanet ID: 342
  SNOMED CT ID: 12579009

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Canakinumab	DM8HLO5	Approved	Antibody	[1]
Colchicine	DM2POTE	Approved	Small molecular drug	[2]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
C5	TTKANGO	Strong	Posttranslational Modification	[3]
C5AR1	TTHXFA1	Strong	Posttranslational Modification	[3]
FCGR1A	TTZK4I3	Strong	Altered Expression	[4]
HBA2	TTQO71U	Strong	Genetic Variation	[5]
KIR2DS1	TTVWAGF	Strong	Biomarker	[6]
KIR2DS2	TTV3CFI	Strong	Biomarker	[6]
KIR3DL2	TTQH3N0	Strong	Biomarker	[6]
LYZ	TTAOZBW	Strong	Biomarker	[7]
MVK	TT5DFHW	Strong	Biomarker	[8]
NLRP3	TT4EN8X	Strong	Biomarker	[9]
PKN1	TTSL41O	Strong	Biomarker	[8]
S100A12	TTQ4ESF	Definitive	Altered Expression	[10]
TNFRSF1A	TTG043C	Definitive	Biomarker	[11]

This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
ABCC6	DT582KR	Strong	Biomarker	[12]

This Disease Is Related to 24 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SAA2	OTYAVJWG	Disputed	Genetic Variation	[13]
SEC23B	OT2NFSIQ	Disputed	CausalMutation	[14]
ADA2	OTGCV24S	Strong	Biomarker	[11]
C5AR2	OTP1Q82J	Strong	Posttranslational Modification	[3]
CARD14	OTADQHOV	Strong	Genetic Variation	[11]
CD1C	OT4XINUJ	Strong	Biomarker	[15]
COL9A1	OTWBR27Y	Strong	Genetic Variation	[16]
COL9A2	OT1ZBDBV	Strong	Genetic Variation	[16]
COL9A3	OTCUJOEK	Strong	Genetic Variation	[16]
ELF4	OT167PR5	Strong	Biomarker	[17]
ERAL1	OTSH78HD	Strong	Genetic Variation	[18]
GSDMD	OTH39BKI	Strong	Biomarker	[19]
HBA1	OTW2BQF4	Strong	Genetic Variation	[5]
KIDINS220	OTLBH2MA	Strong	Genetic Variation	[20]
LPIN2	OTRRTMXX	Strong	Genetic Variation	[21]
NLRP12	OTGR132Z	Strong	Genetic Variation	[9]
PACC1	OTKBS8CC	Strong	Biomarker	[22]
PSTPIP1	OT4PGEAB	Strong	Genetic Variation	[23]
RNPC3	OTW5MKC1	Strong	Genetic Variation	[24]
TRIM21	OTA4UJCF	Strong	Biomarker	[25]
TRIM38	OT6SP1M9	Strong	Genetic Variation	[26]
TRIM5	OTMZH7EJ	Strong	Biomarker	[25]
LMX1B	OTM8145D	Definitive	Genetic Variation	[27]
MEFV	OTRJ6S6K	Definitive	Autosomal recessive	[28]

References

• [1] Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review. Turk J Med Sci. 2020 Nov 3;50(SI-2):1591-1610.
• [2] Colchicine FDA Label
• [3] Genetic analysis of C5a receptors in neutrophils from patients with familial Mediterranean fever.Mol Biol Rep. 2012 May;39(5):5503-10. doi: 10.1007/s11033-011-1353-6. Epub 2011 Dec 21.
• [4] Coexistence of polymyositis and familial Mediterranean fever.Mod Rheumatol. 2013 Mar;23(2):374-8. doi: 10.1007/s10165-012-0649-2. Epub 2012 Apr 25.
• [5] Regional mapping of the gene for familial Mediterranean fever on human chromosome 16p13.Am J Med Genet. 1993 Jul 1;46(6):689-93. doi: 10.1002/ajmg.1320460619.
• [6] Killer Cell Immunoglobulin-Like Receptor (KIR) Genotype Distribution in Familial Mediterranean Fever (FMF) Patients.Med Sci Monit. 2015 Nov 17;21:3547-54. doi: 10.12659/msm.895211.
• [7] Renal amyloidosis as a first manifestation of Familial Mediterranean Fever.Scand J Rheumatol. 2000;29(2):129-30. doi: 10.1080/030097400750001950.
• [8] Pyrin inflammasome activation and RhoA signaling in the autoinflammatory diseases FMF and HIDS.Nat Immunol. 2016 Aug;17(8):914-21. doi: 10.1038/ni.3457. Epub 2016 Jun 6.
• [9] Phenotypes and genotypes of Chinese adult patients with systemic autoinflammatory diseases.Semin Arthritis Rheum. 2019 Dec;49(3):446-452. doi: 10.1016/j.semarthrit.2019.05.002. Epub 2019 May 11.
• [10] S100A12 and vascular endothelial growth factor can differentiate Blau syndrome and familial Mediterranean fever from systemic juvenile idiopathic arthritis.Clin Rheumatol. 2019 Mar;38(3):835-840. doi: 10.1007/s10067-018-4359-9. Epub 2018 Nov 8.
• [11] Diagnostic utility of a targeted next-generation sequencing gene panel in the clinical suspicion of systemic autoinflammatory diseases: a multi-center study.Rheumatol Int. 2019 May;39(5):911-919. doi: 10.1007/s00296-019-04252-5. Epub 2019 Feb 19.
• [12] ABCC6 is unlikely to be a modifier gene for familial Mediterranean fever severity.J Genet. 2007 Dec;86(3):293-5. doi: 10.1007/s12041-007-0040-9.
• [13] MEFV and SAA1 genotype associations with clinical features of familial Mediterranean fever and amyloidosis in Armenia.Clin Exp Rheumatol. 2016 Sep-Oct;34(6 Suppl 102):72-76. Epub 2016 Oct 25.
• [14] Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores.Am J Hematol. 2014 Oct;89(10):E169-75. doi: 10.1002/ajh.23800. Epub 2014 Jul 22.
• [15] Folliculotropic Mycosis Fungoides with Skewed T-cell Receptor CDR3 Motif: Suggestive of Lipid-antigen Selection?.Acta Derm Venereol. 2017 Oct 2;97(9):1081-1086. doi: 10.2340/00015555-2722.
• [16] Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF).Eur J Hum Genet. 1998 Jan;6(1):95-7. doi: 10.1038/sj.ejhg.5200170.
• [17] Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies.Am J Hum Genet. 1993 Aug;53(2):451-61.
• [18] MEFV gene mutations in Turkish children with juvenile idiopathic arthritis.Eur J Pediatr. 2013 Aug;172(8):1061-7. doi: 10.1007/s00431-013-2003-x. Epub 2013 Apr 16.
• [19] GSDMD is critical for autoinflammatory pathology in a mouse model of Familial Mediterranean Fever.J Exp Med. 2018 Jun 4;215(6):1519-1529. doi: 10.1084/jem.20172060. Epub 2018 May 23.
• [20] Clinical and molecular diagnosis of Familial Mediterranean Fever in Egyptian children.J Gastrointestin Liver Dis. 2007 Jun;16(2):141-5.
• [21] Clinical and genetic association, radiological findings and response to biological therapy in seven children from Qatar with non-bacterial osteomyelitis.Int J Rheum Dis. 2017 Sep;20(9):1286-1296. doi: 10.1111/1756-185X.12940. Epub 2016 Nov 9.
• [22] Construction of a 1-Mb restriction-mapped cosmid contig containing the candidate region for the familial Mediterranean fever locus (MEFV) on chromosome 16p 13.3.Genomics. 1997 May 15;42(1):83-95. doi: 10.1006/geno.1997.4629.
• [23] Inflammation in mice ectopically expressing human Pyogenic Arthritis, Pyoderma Gangrenosum, and Acne (PAPA) Syndrome-associated PSTPIP1 A230T mutant proteins.J Biol Chem. 2013 Feb 15;288(7):4594-601. doi: 10.1074/jbc.M112.443077. Epub 2013 Jan 4.
• [24] Determination of autoantibodies in patients with familial Mediterranean fever and their first degree relatives.J Rheumatol. 1991 Apr;18(4):606-8.
• [25] Structural basis for PRYSPRY-mediated tripartite motif (TRIM) protein function.Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6200-5. doi: 10.1073/pnas.0609174104. Epub 2007 Mar 30.
• [26] Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. The International FMF Consortium. Cell. 1997 Aug 22;90(4):797-807. doi: 10.1016/s0092-8674(00)80539-5.
• [27] Co-occurrence of familial Mediterranean fever (FMF) heterozygote mutation and nail-patella syndrome (NPS) in 3 members of a family with LMX1B mutation analysis.Genet Couns. 2007;18(2):259-62.
• [28] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.