| "Diagnosis of Familial Mediterranean Fever by a Molecular Genetics Method" Annals of Internal Medicine, 1 October 1998. 129:539-542. Shlomit Eisenberg, MSc; Ivona Aksentijevich, MD; Zuoming Deng, PhD; Daniel L. Kastner, MD, PhD; and Yaacov Matzner, MD |
BMJ 2000;320:1091-1092 ( 22 April
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Joost P H Drenth and Jos W M van der Meer |
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Mordechai Shohat, MD
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These pages offer excellent (if scientific) means of distinguishing among the several autoimmune hereditary fevers: http://padeh.net/student/Hereditary_autoimmune_fevers.htm http://fmf.igh.cnrs.fr/infevers/page1.html |
| The following is
excerpted from Mordechai Shohat, MD, Rabin Medical Center's article available in full at www.FMFcommunity.org/FMF-FAQ: The diagnosis of familial Mediterranean fever The diagnosis of familial Mediterranean fever (FMF) is suspected in individuals with recurrent episodes of fever associated with abdominal pain (peritonitis) and/or pleuritic pain and/or arthritis (ankle/knee) usually lasting two to three days. Blood tests reveal a high erythrocyte sedimentation rate (ESR), leukocytosis, and a high fibrinogen level. Molecular genetic testing of the MEFV gene (chromosomal locus 16p13.3) usually confirms the diagnosis.
Clinical Diagnosis The features taken into consideration when a diagnosis of FMF is suspected: During the inflammatory attack, the following typically occur: Seventeen mutations have been identified, of which 11 are in exon 10, three in exon 2, two in exon 3, and one in exon 5. These mutations account for most of the disease-causing mutations in the population at risk for FMF (Armenian; Turkish; Arab; North African, Iraqi, and Ashkenazi Jewish; and a few other Mediterranean populations.) A small proportion of patients with FMF have mutations that are not detectable by current mutation analyses or only a single mutation detectable by mutation analysis. |
| Excellent article distinguishing
among several periodic fever diseases, reprinted here from: http://bmj.com/cgi/content/full/320/7242/1091 BMJ 2000;320:1091-1092 ( 22 April ) Editorials Periodic fevers
enter the era of molecular diagnosis
Periodic fever syndromes are a group of disorders characterised by attacks
of fever separated by symptom free intervals. So far four types, all inherited,
have been described. Familial Mediterranean fever
and hyper-IgD and periodic
fever syndrome (hyper-IgD syndrome) are transmitted as autosomal recessive
traits while familial Hibernian fever and Muckle-Wells syndrome are autosomal dominant periodic
fevers. Over the past decade the gene for Muckle-Wells syndrome has been
localised and those for the other three disorders identified. This work has
resulted in better means of diagnosing these rare conditions and has also
thrown new light on the molecular basis of inflammation. And they are throwing some light on inflammatory mechanisms Familial Mediterranean fever is the commonest periodic fever disorder, occurring mainly in people originating from the Mediterranean basin.1 In Israel alone over 5000 people are estimated to suffer from this disorder. Attacks start before the age of 20 and are characterised by short (1-4 days) attacks of fever and serositis. Most patients have recurrent peritonitis, but pleuritis also occurs. Asymmetric monoarthritis of the large joints is common, while an erysipelas-like rash develops less often. Familial Mediterranean fever can be complicated by nephropathic amyloidosis of the AA type, but in most patients colchicine up to 1-2 mg/day prevents both the acute attacks and the development of amyloidosis. Diagnosis is based on clinical manifestations, ethnicity, family history, and response to colchicine.
After initial localisation on the short arm of chromosome 16 (16p13) the gene for familial Mediterranean fever, designated MEFV, was cloned in 1997. 2 3 It encodes a hitherto unknown protein named pyrin-marenostrin. The gene consists of 10 exons, and the genomic sequence of MEFV predicts a protein of 781 amino acid residues which are mainly expressed in granulocytes. Homology studies suggest that pyrin-marenostrin has a role in the autoregulation of inflammation. So far at least 15 mutations have been detected mostly in exon 10 but also in exon 2. The M694V mutation is the most prevalent, being found in about 80% of the familial Mediterranean fever chromosomes.4 Hyper-IgD syndrome occurs as recurrent fever in patients of Western European origin and to date some 140 patients are known. Attacks mostly start under the age of 1 year and the raised serum IgD serves as a biological marker of this syndrome. During episodes lasting 3-7 days patients suffer from abdominal distress (not peritonitis), lymphadenopathy, skin lesions, and arthralgias. Surprisingly, amyloidosis has not been described. The diagnosis is made from the typical clinical picture and a high IgD value.5
The familial occurrence made it possible to use linkage analysis to localise the gene for hyper-IgD syndrome on the long arm of chromosome 12 (12q24).6 This finding and other investigations, which showed a mild mevalonic aciduria with attacks, led to the identification of mevalonate kinase as the hyper-IgD gene. 6 7 Mevalonate kinase follows 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase in cholesterol biosynthesis. In the hyper-IgD syndrome we and others detected several missense mutations in the gene encoding for mevalonate kinase, 6 7 which all result in decreased enzyme activity. It is surprising that a defect in cholesterol metabolism can cause a periodic inflammatory disease, and the connection remains a puzzle. Familial Hibernian fever presents as a vertically transmitted syndrome with fever, abdominal pain, and localised myalgias. Episodic erythematous patches, conjunctivitis, unilateral periorbital oedema, and amyloidosis may occasionally be found. Attacks tend to last longer than in the hyper-IgD syndrome or familial Mediterranean fever. The condition was initially described in one family of Irish descent,8 but similar findings were later found in other families. A breakthrough came when in two separate families linkage was detected with chromosome 12 (12p13). 9 10 The type I tumour necrosis factor receptor appeared a good candidate gene because serum levels are grossly diminished during and between attacks. Indeed in seven different families, six missense mutations in the type I tumour necrosis factor receptor gene were identified, establishing this gene as the causative gene11 and suggesting that attacks result from decreased shedding of tumour necrosis factor receptor from the membrane. This discovery also led to a change of name to tumour necrosis factor-receptor associated periodic syndrome and opened the avenue to treatment with injectable soluble tumour necrosis factor receptor; preliminary experience suggests it might work (Drewe L, Kastner D, 2nd international workshop on hyper-IgD and periodic fever syndrome, Nijmegen, December 1999).
Patients with autosomal dominant Muckle-Wells syndrome suffer from acute febrile attacks with abdominal pain, arthritis, and urticaria sometimes complicated by progressive nerve deafness and multiorgan AA-type amyloidosis. With linkage analysis the gene for Muckle-Wells syndrome was recently localised at chromosome 1q44 and efforts are under way to clone the gene.12 The identification of the periodic fever genes has clear implications. Firstly, it sheds important new light on the molecular basis of inflammation and illustrates the exhaustive repertoire of inflammatory response in humans. Secondly, knowledge on correlates between genotypes and phenotypes influences patient care. For example, homozygosity for the M694V mutation is strongly associated with the development of amyloidosis, emphasising the need for early treatment with colchicine in these patients.13 Lastly, until recently the diagnosis of a periodic fever syndrome was made solely on clinical grounds, which can be difficult in some (non-familial) cases. With the discovery of the implicated genes, molecular testing becomes possible. Several service laboratories in the United Kingdom provide testing for familial Mediterranean fever. Nevertheless, rapid screening tests screen only for known mutations, and in some patients with a very typical clinical picture even advanced molecular tools may fail to detect mutations. In familial Mediterranean fever, for example, a genetic diagnosis will be made in only 65-94% of typical cases, even after thorough testing.14 Until the full mutational spectrum of these periodic fever genes are known clinicians should continue to make the diagnosis on clinical grounds and use the molecular test only as a useful adjunct.
Joost P H Drenth, resident in internal medicine. Jos W M van der Meer, professor of internal medicine. Department of Medicine, University Hospital St Radboud, PO Box 9101, 6500 HB Nijmegen, Netherlands (JPHDrenth@compuserve.com) -------------------------------------------------------------------------------- 1. Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet 1998; 351: 659-664. 2. The French FMF Consortium. A candidate gene for familial Mediterranean fever. Nat Genet 1997; 17: 25-31. 3. The International FMF Consortium. Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 1997; 90: 797-807. 4. Aksentijevich I, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, 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. Am J Hum Genet 1999; 64: 949-962. 5. Drenth JP, Haagsma CJ, van der Meer JW. Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients. International Hyper-IgD Study Group. Medicine 1994; 73: 133-144. 6. Drenth JP, Cuisset L, Grateau G, Vasseur C, van der Velde Visser SD, de Jong JG, et al. Mutations in the gene encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 1999; 22: 178-181.
7. Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, et al. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nat Genet 1999; 22: 175-177. 8. McDermott EM, Smillie DM, Powell RJ. Clinical spectrum of familial Hibernian fever: a 14-year follow-up study of the index case and extended family. Mayo Clin Proc 1997; 72: 806-817. 9. McDermott MF, Ogunkolade BW, McDermott EM, Jones LC, Wan Y, Quane KA, et al. Linkage of familial Hibernian fever to chromosome 12p13. Am J Hum Genet 1998; 62: 1446-1451. 10. Mulley J, Saar K, Hewitt G, Ruchendorf F, Phillips H, Colley A, et al. Gene localization for an autosomal dominant familial periodic fever to 12p13. Am J Hum Genet 1998; 62: 884-889. 11. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 1999; 97: 133-144.
12. Cuisset L, Drenth JP, Berthelot JM, Meyrier A, Vaudour G, Watts RA, et al. Genetic linkage of the Muckle-Wells syndrome to chromosome 1q44. Am J Hum Genet 1999; 65: 1054-1059. 13. Livneh A, Langevitz P, Shinar Y, Zaks N, Kastner DL, Pras M, et al. MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever. Amyloid 1999; 6: 1-6. 14. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 25-1999. A 16-year-old boy with recurrent abdominal pain . N Engl J Med 1999;341:593-9. -------------------------------------------------------------------------------- © BMJ 2000 This article has been cited by other articles: A. Simon, M. van Deuren, P. J. Tighe, J. W. M. van der Meer, and J. P. H. Drenth Genetic Analysis as a Valuable Key to Diagnosis and Treatment of Periodic Fever Archives of Internal Medicine, November 12, 2001; 161(20): 2491 - 2493. -------------------------------------------------------------------------------- J. P. H. Drenth, A. G. Vonk, A. Simon, R. Powell, and J. W. M. van der Meer Limited Efficacy of Thalidomide in the Treatment of Febrile Attacks of the Hyper-IgD and Periodic Fever Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1221 - 1226. -------------------------------------------------------------------------------- D C W Poland, J P H Drenth, E Rabinovitz, A Livneh, J Bijzet, B van het Hof, and W van Dijk Specific glycosylation of {alpha}1-acid glycoprotein characterises patients with familial Mediterranean fever and obligatory carriers of MEFV Ann. Rheum. Dis, August 1, 2001; 60(8): 777 - 780. -------------------------------------------------------------------------------- © 2003 BMJ Publishing Group Ltd
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Annals of Internal Medicine, 1 October 1998. 129:539-542. Shlomit Eisenberg, MSc; Ivona Aksentijevich, MD; Zuoming Deng, PhD; Daniel L. Kastner, MD, PhD; and Yaacov Matzner, MD Background: Familial Mediterranean fever is a recessively inherited disorder characterized by episodes of fever with abdominal pain, pleurisy, or arthritis. The familial Mediterranean fever gene, designated MEFV, was recently cloned, and at least three missense mutations (M680I, M694V, and V726A) that account for a large percentage of patients with this disease were identified. Objective: To establish a diagnostic test for familial Mediterranean fever. Design: Cross-sectional study of a convenience sample of patients attending familial Mediterranean fever clinics. Setting: Tertiary referral hospitals. Patients: 107 patients with familial Mediterranean fever, their family members, and controls. Measurements: Mutations in the 107 samples were assessed by amplifying genomic DNA with use of primers that selectively amplify the normal or altered DNA sequence of the 3 MEFV mutations (amplification refractory mutation system [ARMS]). Mutations were independently assessed by automated sequencing of genomic DNA amplified by polymerase chain reaction to evaluate the sensitivity and specificity of the ARMS assay. Results: The ARMS assay correctly identified M680I, M694V, and V726A mutations in 82 persons with mutations documented by DNA sequencing (21 homozygotes, 2 compound heterozygotes, and 59 simple heterozygotes). Of 7 persons known from family studies to be noncarriers and 18 unrelated persons who were negative for these mutations by sequencing, none had MEFV mutations according to ARMS. Conclusion: The ARMS assay is a rapid, cost-effective, and accurate method for detecting three common mutations in familial Mediterranean fever. Ann Intern Med. 1998;129:539-542. Annals of Internal Medicine is published twice monthly and copyrighted © 1998 by the American College of Physicians-American Society of Internal Medicine. From Hadassah University Hospital, Mount Scopus, Jerusalem, Israel; and the Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland. For current author addresses, see end of text.
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Familial Mediterranean fever, or recurrent polyserositis, is a recessively inherited disorder that affects Sephardic Jews, Turks, Armenians, and Arabs. In these populations, the carrier frequency has been estimated to be as high as 1 in 5 persons (1, 2). The disorder is characterized by recurrent episodes of unprovoked inflammation involving the joints; the pleural and peritoneal cavities; and, less frequently, the skin. Familial Mediterranean fever peritonitis, the most common manifestation of this disease, may resemble acute abdomen, leading to laparotomy and appendectomy that reveal only an inflamed peritoneum and a neutrophilic exudate. If a surgical procedure is avoided, the attack resolves spontaneously (3-7). Patients are treated with colchicine, a neutrophil-suppressive agent that has been shown to decrease the frequency and severity of attacks when administered on a long-term basis (8, 9). Some patients develop amyloidosis that can also be prevented by prophylactic colchicine administration (10). The diagnosis of familial Mediterranean fever requires a high index of suspicion and is based on the clinical criteria of acute, reversible serosal attack and family history, when available. Until recently, the only specific laboratory test for this disease was the documentation of C5a-inhibitor deficiency in serosal or synovial fluid, a laborious assay that requires an invasive procedure (11-13).
The gene responsible for familial Mediterranean fever, designated MEFV, was recently cloned (14, 15). Its protein product pyrin-marenostrin was found by computer alignment to be homologous with previously described nuclear factors that may play a role in the regulation of inflammatory processes. Several missense mutations were identified, accounting for a large percentage of patients with familial Mediterranean fever, but these mutations were absent in all normal persons studied. As a result, it is highly likely that mutations of MEFV are responsible for familial Mediterranean fever. We describe a rapid and accurate method for establishing the molecular diagnosis of familial Mediterranean fever, based on polymerase chain reaction (PCR) amplification of three common mutations—M680I, M694V, and V726A—in this newly cloned gene. Methods Patients and DNA Samples We obtained DNA samples from 107 persons. A total of 74 persons from 44 families gave specimens at the Sheba Medical Center in Tel Hashomer, Israel, as part of the project to identify the familial Mediterranean fever gene by positional cloning. Forty-three of these families were of non-Ashkenazi Jewish ancestry, and one family was Druze. Of the 74 family members, 19 had familial Mediterranean fever according to established clinical criteria (16), 48 were unaffected but were familial Mediterranean fever carriers according to haplotype analysis, and 7 were unaffected and were noncarriers according to haplotype analysis. Two persons (1 affected person and 1 asymptomatic carrier) from 1 Armenian-American family also gave blood as part of the same positional cloning project at the Cedars-Sinai Medical Center. Thirty-one additional persons gave or sent samples to the National Institutes of Health for genetic testing after the familial Mediterranean fever gene had been identified. Of these 31 persons, 27 had undiagnosed fever syndromes and 4 were unaffected family members. By DNA sequencing, 1 person was an M694V homozygote, 2 were M694V/M680I compound heterozygotes, 6 were symptomatic but had only one copy of the three mutations, and 4 were asymptomatic heterozygote carriers. The remaining 18 persons were negative for all three mutations by DNA sequencing.
Informed consent of the participants in the study was obtained after approval by the human experimentation committee at each institution. Standard techniques were used to extract DNA from whole blood or from Epstein-Barr virus-transformed lymphocytes (17). Mutation Detection by the Amplification Refractory Mutation System The amplification refractory mutation system (ARMS) assay comprises two complementary reactions, each conducted with the same substrate DNA. One reaction includes an ARMS primer specific for the normal DNA sequence and cannot amplify mutant DNA at a given locus. The second reaction includes a mutant-specific primer and cannot amplify normal DNA. The same common primer is used in both reactions (17, 18). The lack of PCR products according to use of a specific mutation primer set in patients suspected of carrying the mutation for familial Mediterranean fever suggests that the patient in question is not carrying the mutation being probed. However, an appropriate internal PCR control should be run to show that the DNA is amplifiable. Therefore, the complementary reaction with the normal primer set serves as an internal control for PCR amplification and allows discrimination of homozygotes from heterozygotes.
Mutations were assessed by amplifying the genomic DNA template with three sets of normal and mutant-specific ARMS primers designed to selectively amplify the normal or altered sequence of each of the three MEFV mutations. Each set of primers consisted of three oligonucleotides. For mutation M680I, the sequences were 5'-TTAGACTTGGAAACAAGTGGGAGAGGCTGC-3' (common), 5'-ATTATCACCACCCAGTAGCCATTCTCTGGC-GACAGAGCG-3' (mutant), and 5'-ATTATCACCACCCAGTAGCCATTCTCTGGCGACAGAGCC-3' (normal); for M694V, they were 5'-TGACAGCTGTATCATTGTTCTGGGCTCTCCG-3' (common), 5'-TCGGGGGAACGCTGGACGCCTGGTACTCAT-TTTCCTTCCC-3' (mutant), and 5'-TCGGGGGAACGCTGGACGCCTGGTACTCATTTTCCTTCCT-3' (normal); and for V726A, they were 5'-TGGAGGTTGGAGACAAGACAGCATGGATCC-3' (common), 5'-TGGGATCTGGCTGTCACATTGTAAAAGGAGATGCTTCCTG-3' (mutant), and 5'-TGGGATCTGGCTGTCACATTGTAAAAGGAGATGCTTCCTA-3' (normal). Each DNA sample was tested for the three mutations. The PCR amplification was performed in a final volume of 25 µL containing 100 ng of purified genomic DNA, 0.04 U of Ampli Taq Gold (Perkin-Elmer, Branchburg, New Jersey) and its 1× PCR buffer (contains 15 mmol of MgCl2 per L), 0.2 mmol of deoxynucleoside 5'-triphosphate mix per L (Gibco BRL, Gaithersburg, Maryland), and 1 pmol of each primer. Amplification conditions were kept the same for all of the ARMS tests, and the procedure was carried out as follows. The reaction was heated to 94 °C for 9 minutes for denaturation, followed by 35 cycles with denaturation at 94 °C for 10 seconds, annealing at 60 °C for 10 seconds, and extension at 72 °C for 30 seconds. Final extension was done for 10 minutes at 72 °C. The amplified products were separated by electrophoresis on a 2% agarose gel. Ethidium bromide staining of the agarose gel was used to detect the amplified fragments.
Results Samples of DNA from persons affected by familial Mediterranean fever, their relatives, and normal controls were screened to determine mutation status. The results of a representative assay for each mutation are shown in the Figure. A summary of the results obtained for the study group is shown in the Table. For 82 samples that were studied, all three mutations were found in accordance with mutation status. None of these mutations was identified in the remaining 25 samples, as predicted by previous sequencing analysis. The most frequent mutation in our predominantly non-Ashkenazi Jewish panel was M694V. All persons with the M680I mutation were of Armenian ancestry, whereas the V726A mutation was found in Armenians, Ashkenazi Jews, and Iraqi Jews. No false-positive or false-negative results were obtained by using the three sets of primers for each sample, indicating a sensitivity and specificity of 100% for this assay. Discussion We describe a simple, rapid, and highly reliable method for establishing the molecular diagnosis of familial Mediterranean fever, a disease primarily diagnosed on a clinical basis (3-7). The results were validated by analyzing previously genotyped samples and proved to be totally accurate. For 107 samples that were independently genotyped by automatic sequencing as part of the project to identify the familial Mediterranean fever gene by positional cloning (14), no false-positive or false-negative results were obtained with the ARMS assay.
The ARMS assay used for molecular diagnosis in our study allows accurate detection of haplotypes with mutations involving single-base changes or small deletions (18, 19). We developed a single ARMS assay for detection of the three most common MEFV point mutations described during the cloning of the familial Mediterranean fever gene (14, 15). In addition to the reliability of the ARMS assay, several practical considerations associated with this assay may be of interest. First, genomic DNA or, alternatively, crude cell lysate of leukocytes is used as a source of template DNA. Second, it is not necessary to prepare high-quality DNA suitable for restriction enzyme digestion. Finally, the use of radioactive materials is not required. Moreover, additional mutations could be studied by using the same method; the three disease-associated mutations discussed here do not account for all familial Mediterranean fever carrier chromosomes, and at least eight additional mutations are under study (20; Aksentijevich et al. In preparation). It seems that about 70% of carrier chromosomes from non-Ashkenazi Jews in Israel bear the M694V or V726A mutation. A population study that should clarify this issue is already under way. In a recent study of Turkish familial Mediterranean fever (21), the three mutations presented here accounted for 29 of 34 disease alleles. The occurrence of these mutations in the United States may be somewhat lower (20). In persons with suggestive clinical and family history but no documented common mutation, an ARMS assay with additional sets of primers designed for other mutations or complete sequencing of the MEFV gene is indicated.
Accurate diagnosis of familial Mediterranean fever is important not only for genetic consultation and avoidance of unnecessary colchicine therapy but also for prevention of avoidable laparotomies due to misdiagnosed acute abdomen. Moreover, some patients develop amyloidosis early in the course of the attacks of familial Mediterranean fever (type II) (6), and proper genetic consultation may suggest early introduction of colchicine in these cases. The rapid, cost-effective ($150 according to Hadassah Hospital estimates), and highly reliable ARMS assay allows fast detection of the familial Mediterranean fever mutations prevalent in Israel. It enables early molecular confirmation of suspected cases of familial Mediterranean fever, thus preventing undesirable abdominal surgery and unnecessary colchicine therapy. In addition, it enables rapid typing of patients with familial Mediterranean fever and their relatives, thereby allowing proper genetic and therapeutic consultation, especially when early amyloidosis is suspected. Acknowledgments: The authors thank Dr. M. Pras, Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel, for providing many of the DNA samples used in this study; Dr. N. Fischel-Ghodsian, Cedars-Sinai Medical Center, Los Angeles, for providing the two Armenian DNA samples; and Dr. Alexandra Mahler for critical review of the manuscript. Grant Support: By grant 95-00588 from the United States-Israel Binational Science Foundation and grant 3191 provided by the chief scientist, Ministry of Health, Israel, to Dr. Matzner. Requests for Reprints: Yaacov Matzner, MD, Hematology Unit, Hadassah University Hospital, Mount Scopus, Jerusalem, 91240; e-mail, matzner@cc.huji.ac.il Current Author Addresses: Ms. Eisenberg and Dr. Matzner: Hematology Unit, Hadassah University Hospital, Mount Scopus, Jerusalem, 91240. Drs. Aksentijevich, Deng, and Kastner: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892.
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References 1. Rogers DB, Shohat M, Petersen GM, Bickal J, Congleton J, Schwabe AD, et al. Familial Mediterranean fever in Armenians: autosomal recessive inheritance with high gene frequency. Am J Med Genet. 1989;34:168-72. 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;55:311-4. 3. Siegal S. Benign paroxysmal peritonitis. Ann Intern Med. 1945;23:1-21. 4. Reiman HA. Periodic disease. Probable syndrome including periodic fever, benign paroxysmal peritonitis, cyclic neutropenia and intermittent arthralgia. JAMA. 1948;136:239-44. 5. Heller H, Sohar E, Sherf L. Familial Mediterranean fever. Arch Intern Med. 1958;102:50-71. 6. 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;43:227-53. 7. Matzner Y. Biologic and clinical advances in familial Mediterranean fever. Crit Rev Oncol Hematol. 1995;18:197-205. 8. Zemer D, Revach M, Pras M, Modan B, Schor S, Sohar E, et al. A controlled trial of colchicine in preventing attacks of familial Mediterranean fever. N Engl J Med. 1974;291:932-4. 9. Dinarello CA, Wolff SM, Goldfinger SE, Dale DC, Alling DW. Colchicine therapy for familial Mediterranean fever. A double-blind trial. N Engl J Med. 1974;291:934-7. 10. 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;314:1001-5. 11. Matzner Y, Brzezinski A. C5a-inhibitor deficiency in peritoneal fluids from patients with familial Mediterranean fever. N Engl J Med. 1984;311:287-90. 12. Matzner Y, Partridge RE, Levy M, Babior BM. Diminished activity of a chemotactic inhibitor in synovial fluids from patients with familial Mediterranean fever. Blood. 1984;63:629-33. 13. Matzner Y, Ayesh S, Hochner-Celniker D, Ackerman Z, Ferne M. Proposed mechanism of the inflammatory attacks in familial Mediterranean fever. Arch Intern Med. 1990;150:1289-91. 14. 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;90:797-807. 15. A candidate gene for familial Mediterranean fever. The French FMF Consortium. Nat Genet. 1997;17:25-31. 16. Livneh A, Langevitz P, Zemer D, Zaks N, Kees S, Lidar T, et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum. 1997;40:1879-85. 17. Clinical molecular genetics. Amplification Refractory Mutation System (ARMS) analysis of point mutations. In: Dracopoli NC, Haines JL, Korf BR, et al, eds. Current Protocols in Human Genetics. New York: J Wiley; 1995:9.8.1-9.8.12. 18. Ferrie RM, Schwarz MJ, Robertson NH, Vaudin S, Super M, Malone G, et al. Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene. Am J Hum Genet. 1992;51:251-62. 19. Newton CR, Graham A, Heptinstall LE, Powell SJ, Summers C, Kalsheker N, et al. Analysis of any point mutation in DNA. The amplification refractory mutation system (ARMS). Nucleic Acids Res. 1989;17:2503-16. 20. Samuels J, Aksentijevich I, Torosyan Y, Centola M, Deng Z, Sood R, et al. Familial Mediterranean fever at the millenium: clinical spectrum, ancient mutations, and a survey of 100 American referrals to the National Institutes of Health. Medicine (Baltimore). 1998;77:268-97. 21. Chen X, Fischel-Ghodsian N, Cercek A, Hamon M, Ogur G, Lotan R, et al. Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF). Hum Mutat. 1998;11:456-60. |
