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. 1997 May;34(5):375–381. doi: 10.1136/jmg.34.5.375

Genotypic diagnosis of familial Mediterranean fever (FMF) using new microsatellite markers: example of two extensive non-Ashkenazi Jewish pedigrees.

M Dupont 1, C Dross 1, N Smaoui 1, B Nedelec 1, G Grateau 1, C Clépet 1, I Gourdier 1, I Koné-Paut 1, M Delpech 1, J Demaille 1, I Touitou 1
PMCID: PMC1050944  PMID: 9152834

Abstract

Familial Mediterranean fever is an autosomal recessive disease characterised by multiple attacks of serosal inflammation in the absence of treatment. In the absence of timely diagnosis, renal amyloidosis is a life threatening complication. The diagnosis is often missed because no specific test is available. Early colchicine treatment prevents attacks and renal complications. The FMF gene (MEF) has been mapped to chromosome 16p 13.3 but has not yet been identified. We compared the suitability of a series of microsatellite markers (four of them were new) and propose the routine use of seven of these markers, exhibiting alleles in strong linkage disequilibrium with the disease and informative in 100% of diagnosed patients. Moreover, the discovery of a homozygous status for the 3-3-9 (or 3-3-18) haplotype at the core loci (D16S3070, D16S3082, and D16S3275), which was found in 73% non-Ashkenazi Jewish patients, points to a diagnosis of FMF, even in sporadic cases, with a risk of error of only 2.10(-5). Two extensive pedigrees covering most indications for genetic counselling are presented, showing that it is now possible both prospectively and retrospectively to identify members likely to have MEF mutations. With the help of this accurate test, colchicine treatment can be better targeted, especially where the symptomatology is mild or atypical.

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Selected References

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  1. Aksentijevich I., Pras E., Gruberg L., Shen Y., Holman K., Helling S., Prosen L., Sutherland G. R., Richards R. I., Ramsburg M. Refined mapping of the gene causing familial Mediterranean fever, by linkage and homozygosity studies. Am J Hum Genet. 1993 Aug;53(2):451–461. [PMC free article] [PubMed] [Google Scholar]
  2. Daniels M., Shohat T., Brenner-Ullman A., Shohat M. Familial Mediterranean fever: high gene frequency among the non-Ashkenazic and Ashkenazic Jewish populations in Israel. Am J Med Genet. 1995 Jan 30;55(3):311–314. doi: 10.1002/ajmg.1320550313. [DOI] [PubMed] [Google Scholar]
  3. Gyapay G., Morissette J., Vignal A., Dib C., Fizames C., Millasseau P., Marc S., Bernardi G., Lathrop M., Weissenbach J. The 1993-94 Généthon human genetic linkage map. Nat Genet. 1994 Jun;7(2 Spec No):246–339. doi: 10.1038/ng0694supp-246. [DOI] [PubMed] [Google Scholar]
  4. HELLER H., SOHAR E., SHERF L. Familial Mediterranean fever. AMA Arch Intern Med. 1958 Jul;102(1):50–71. doi: 10.1001/archinte.1958.00260190052007. [DOI] [PubMed] [Google Scholar]
  5. Højberg A. S., Mertz H. Nefrotisk syndrom ved familiaer middelhavsfeber--effekt af colchicinbehandling. Ugeskr Laeger. 1995 Jul 10;157(28):4035–4037. [PubMed] [Google Scholar]
  6. Livneh A., Zemer D., Langevitz P., Laor A., Sohar E., Pras M. Colchicine treatment of AA amyloidosis of familial Mediterranean fever. An analysis of factors affecting outcome. Arthritis Rheum. 1994 Dec;37(12):1804–1811. doi: 10.1002/art.1780371215. [DOI] [PubMed] [Google Scholar]
  7. Localization of the familial Mediterranean fever gene (FMF) to a 250-kb interval in non-Ashkenazi Jewish founder haplotypes. The French FMF Consortium. Am J Hum Genet. 1996 Sep;59(3):603–612. [PMC free article] [PubMed] [Google Scholar]
  8. Pras E., Aksentijevich I., Gruberg L., Balow J. E., Jr, Prosen L., Dean M., Steinberg A. D., Pras M., Kastner D. L. Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16. N Engl J Med. 1992 Jun 4;326(23):1509–1513. doi: 10.1056/NEJM199206043262301. [DOI] [PubMed] [Google Scholar]
  9. Rogers D. B., Shohat M., Petersen G. M., Bickal J., Congleton J., Schwabe A. D., Rotter J. I. Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. Am J Med Genet. 1989 Oct;34(2):168–172. doi: 10.1002/ajmg.1320340206. [DOI] [PubMed] [Google Scholar]
  10. Rozenbaum M., Rosner I. Regression of amyloidosis with colchicine in familial Mediterranean fever in an Ashkenazi patient. Clin Exp Rheumatol. 1995 Jan-Feb;13(1):126–126. [PubMed] [Google Scholar]
  11. Shohat M., Bu X., Shohat T., Fischel-Ghodsian N., Magal N., Nakamura Y., Schwabe A. D., Schlezinger M., Danon Y., Rotter J. I. The gene for familial Mediterranean fever in both Armenians and non-Ashkenazi Jews is linked to the alpha-globin complex on 16p: evidence for locus homogeneity. Am J Hum Genet. 1992 Dec;51(6):1349–1354. [PMC free article] [PubMed] [Google Scholar]
  12. Sohar E., Gafni J., Pras M., Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med. 1967 Aug;43(2):227–253. doi: 10.1016/0002-9343(67)90167-2. [DOI] [PubMed] [Google Scholar]
  13. Yuval Y., Hemo-Zisser M., Zemer D., Sohar E., Pras M. Dominant inheritance in two families with familial Mediterranean fever (FMF). Am J Med Genet. 1995 Jul 3;57(3):455–457. doi: 10.1002/ajmg.1320570319. [DOI] [PubMed] [Google Scholar]
  14. Zemer D., Pras M., Sohar E., Modan M., Cabili S., Gafni J. Colchicine in the prevention and treatment of the amyloidosis of familial Mediterranean fever. N Engl J Med. 1986 Apr 17;314(16):1001–1005. doi: 10.1056/NEJM198604173141601. [DOI] [PubMed] [Google Scholar]

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