Clinical versus genetic diagnosis of familial Mediterranean fever.

The diagnosis of familial Mediterranean fever (FMF) has until recently been based on clinical signs alone. Discovery of the MEFV gene has enabled a molecular approach to diagnosis, which is already well established for diagnosing typical clinical forms of FMF. We evaluated the utility of this molecular approach in a large series of patients with various clinical presentations and ethnic origins. We looked for mutations in the MEFV gene in 303 unselected consecutive patients with a variable (from high to low) clinical suspicion of FMF. Two mutations were found in 133 patients (44%). In 22 patients (7%), the clinical diagnosis of FMF was unlikely according to the Tel Hashomer clinical criteria. Our results suggest that the spectrum of FMF-associated signs is broader than previously believed. Wider indications for genotyping should lead to more frequent diagnosis of FMF.

[1]  J. Kouyoumdjian,et al.  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. , 1999, American journal of human genetics.

[2]  Joost P.H. Drenth,et al.  Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome , 1999, Nature Genetics.

[3]  Ian Todd,et al.  Germline Mutations in the Extracellular Domains of the 55 kDa TNF Receptor, TNFR1, Define a Family of Dominantly Inherited Autoinflammatory Syndromes , 1999, Cell.

[4]  H. Ostrer,et al.  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. , 1999, American journal of human genetics.

[5]  T. Shohat,et al.  Phenotype–genotype correlation in familial Mediterranean fever: evidence for an association between Met694Val and amyloidosis , 1999, European Journal of Human Genetics.

[6]  K. Dahan,et al.  Non-Mediterranean periodic fever , 1999, The Lancet.

[7]  D. Booth,et al.  Pyrin/marenostrin mutations in familial Mediterranean fever. , 1998, QJM : monthly journal of the Association of Physicians.

[8]  J. Weissenbach,et al.  Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). , 1998, Human molecular genetics.

[9]  D. Kastner,et al.  Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. , 1998, Medicine.

[10]  E. Ben-Chetrit,et al.  Familial Mediterranean fever , 1998, The Lancet.

[11]  D. Zemer,et al.  Criteria for the diagnosis of familial Mediterranean fever. , 1997, Arthritis and rheumatism.

[12]  R. Powell,et al.  Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family. , 1997, Mayo Clinic proceedings.

[13]  Jacques Demaille,et al.  A candidate gene for familial Mediterranean fever , 1997, Nature Genetics.

[14]  F. Collins,et al.  Ancient Missense Mutations in a New Member of the RoRet Gene Family Are Likely to Cause Familial Mediterranean Fever , 1997, Cell.

[15]  A. Bakkaloğlu,et al.  Genetic linkage study of familial Mediterranean fever (FMF) to 16p13.3 and evidence for genetic heterogeneity in the Turkish population. , 1997, Journal of medical genetics.

[16]  T. Shohat,et al.  Familial Mediterranean fever: high gene frequency among the non-Ashkenazic and Ashkenazic Jewish populations in Israel. , 1995, American journal of medical genetics.

[17]  J. Rotter,et al.  Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. , 1989, American journal of medical genetics.

[18]  D. Zemer,et al.  Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. , 1986, The New England journal of medicine.

[19]  E. Sohar,et al.  FAMILIAL MEDITERRANEAN FEVER , 1959, Definitions.

[20]  M. Pras,et al.  MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. , 1999, Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis.

[21]  M. Pras.  Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene. , 1998, Scandinavian journal of rheumatology.