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

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1999 Jun 12

PMID 10364520

Citations 51

Authors

C Cazeneuve

T Sarkisian

C Pecheux

M Dervichian

B Nedelec

P Reinert

A Ayvazyan

J C Kouyoumdjian

H Ajrapetyan

M Delpech

M Goossens

C Dode

G Grateau

S Amselem

Affiliations

Soon will be listed here.

Abstract

Familial Mediterranean fever (FMF) is a recessively inherited disorder that is common in patients of Armenian ancestry. To date, its diagnosis, which can be made only retrospectively, is one of exclusion, based entirely on nonspecific clinical signs that result from serosal inflammation and that may lead to unnecessary surgery. Renal amyloidosis, prevented by colchicine, is the most severe complication of FMF, a disorder associated with mutations in the MEFV gene. To evaluate the diagnostic and prognostic value of MEFV-gene analysis, we investigated 90 Armenian FMF patients from 77 unrelated families that were not selected through genetic-linkage analysis. Eight mutations, one of which (R408Q) is new, were found to account for 93% of the 163 independent FMF alleles, with both FMF alleles identified in 89% of the patients. In several instances, family studies provided molecular evidence for pseudodominant transmission and incomplete penetrance of the disease phenotype. The M694V homozygous genotype was found to be associated with a higher prevalence of renal amyloidosis and arthritis, compared with other genotypes (P=.0002 and P=.006, respectively). The demonstration of both the diagnostic and prognostic value of MEFV analysis and particular modes of inheritance should lead to new ways for management of FMF-including genetic counseling and therapeutic decisions in affected families.

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References

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; 43(2):227-53. DOI: 10.1016/0002-9343(67)90167-2. View

Blum A, Gafni J, SOHAR E, SHIBOLET S, Heller H . Amyloidosis as the sole manifestation of familial Mediterranean fever (FMF). Further evidence of its genetic nature. Ann Intern Med. 1962; 57:795-9. DOI: 10.7326/0003-4819-57-5-795. View

Dinarello C, Wolff S, GOLDFINGER S, Dale D, Alling D . Colchicine therapy for familial mediterranean fever. A double-blind trial. N Engl J Med. 1974; 291(18):934-7. DOI: 10.1056/NEJM197410312911804. View

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; 314(16):1001-5. DOI: 10.1056/NEJM198604173141601. View

Patarca R, Freeman G, Schwartz J, Singh R, Kong Q, Murphy E . rpt-1, an intracellular protein from helper/inducer T cells that regulates gene expression of interleukin 2 receptor and human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1988; 85(8):2733-7. PMC: 280073. DOI: 10.1073/pnas.85.8.2733. View

Rogers D, Shohat M, Petersen G, Bickal J, Congleton J, SCHWABE A . Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. Am J Med Genet. 1989; 34(2):168-72. DOI: 10.1002/ajmg.1320340206. View

Pras E, Aksentijevich I, Gruberg L, Balow Jr J, Prosen L, Dean M . Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16. N Engl J Med. 1992; 326(23):1509-13. DOI: 10.1056/NEJM199206043262301. View

Reddy B, Etkin L, Freemont P . A novel zinc finger coiled-coil domain in a family of nuclear proteins. Trends Biochem Sci. 1992; 17(9):344-5. DOI: 10.1016/0968-0004(92)90308-v. View

Tissot C, Mechti N . Molecular cloning of a new interferon-induced factor that represses human immunodeficiency virus type 1 long terminal repeat expression. J Biol Chem. 1995; 270(25):14891-8. DOI: 10.1074/jbc.270.25.14891. View

10.

Yuval Y, Zemer D, SOHAR E, Pras M . Dominant inheritance in two families with familial Mediterranean fever (FMF). Am J Med Genet. 1995; 57(3):455-7. DOI: 10.1002/ajmg.1320570319. View

11.

Levy E, Shen Y, Kupelian A, Kruglyak L, Aksentijevich I, Pras E . Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246. Am J Hum Genet. 1996; 58(3):523-34. PMC: 1914560. View

12.

Cotton R . Slowly but surely towards better scanning for mutations. Trends Genet. 1997; 13(2):43-6. DOI: 10.1016/s0168-9525(97)01011-1. View

13.

Saatci U, Ozen S, Ozdemir S, Bakkaloglu A, Besbas N, Topaloglu R . Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis. Eur J Pediatr. 1997; 156(8):619-23. DOI: 10.1007/s004310050677. View

14.

Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T . Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997; 40(10):1879-85. DOI: 10.1002/art.1780401023. View

15.

Quaderi N, Schweiger S, Gaudenz K, Franco B, Rugarli E, Berger W . Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet. 1997; 17(3):285-91. DOI: 10.1038/ng1197-285. View

16.

Bernot A, Da Silva C, PETIT J, Cruaud C, Caloustian C, Castet V . Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet. 1998; 7(8):1317-25. DOI: 10.1093/hmg/7.8.1317. View

17.

Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R . Familial Mediterranean fever at the millennium. Clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore). 1998; 77(4):268-97. DOI: 10.1097/00005792-199807000-00005. View

18.

Eisenberg S, Aksentijevich I, Deng Z, Kastner D, Matzner Y . Diagnosis of familial Mediterranean fever by a molecular genetics method. Ann Intern Med. 1998; 129(7):539-42. DOI: 10.7326/0003-4819-129-7-199810010-00005. View

19.

Dewalle M, Domingo C, Rozenbaum M, Ben-Chetrit E, Cattan D, Bernot A . Phenotype-genotype correlation in Jewish patients suffering from familial Mediterranean fever (FMF). Eur J Hum Genet. 1998; 6(1):95-7. DOI: 10.1038/sj.ejhg.5200170. View

20.

Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae J . 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. Am J Hum Genet. 1999; 64(4):949-62. PMC: 1377819. DOI: 10.1086/302327. View