title: Familial Mediterranean fever without MEFV mutations: a case-control study.
abstract: BACKGROUND
  Although familial Mediterranean fever (FMF) was originally defined as an autosomal recessive disorder, approximately 10-20% of FMF patients do not carry any FMF gene (MEFV) mutations. Fine phenotype characterization may facilitate the elucidation of the genetic background of the so called "FMF without MEFV mutations". In this study we clinically and demographically characterize this subset.
  
  
  METHODS
  MEFV mutation-negative FMF and control patients were recruited randomly from a cohort followed in a dedicated FMF clinic. The control subjects comprised 2 groups: 1. typical population of FMF, consisting of genetically heterogeneous patients manifesting the classical spectrum of FMF phenotype and 2. a severe phenotype of FMF, consisting of FMF patients homozygous for the p.M694V mutation.
  
  
  RESULTS
  Forty-seven genetic-negative, 60 genetically heterogeneous and 57 p.M694V homozygous FMF patients were enrolled to the study. MEFV-mutation negative FMF patients showed a phenotype closely resembling that of the other 2 populations. It differed however from the p.M694V homozygous subset by its milder severity (using Mor et al. scoring method), as determined by the lower proportion of patients with chest and erysipelas like attacks, lower frequency of some of the chronic manifestations, lower colchicine dose and older age of disease onset.
  
  
  CONCLUSIONS
  MEFV mutation-negative FMF by virtue of its classical FMF phenotype is probably associated with a genetic defect upstream or downstream to MEFV related metabolic pathway.
authors.affiliation: Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Ilan.Benzvi@sheba.health.gov.il.|The Rheumatology unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Ilan.Benzvi@sheba.health.gov.il.|Heller Institute of Medical research, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Ilan.Benzvi@sheba.health.gov.il.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Ilan.Benzvi@sheba.health.gov.il.|The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel. Ilan.Benzvi@sheba.health.gov.il.
authors.forename: Ilan
authors.initials: I
authors.lastname: Ben-Zvi
authors.affiliation: Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. corinne.del@gmail.com.
authors.forename: Corinne
authors.initials: C
authors.lastname: Herskovizh
authors.affiliation: Institute of Nephrology and Hypertension, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Olga.Kokoi@sheba.health.gov.il.
authors.forename: Olga
authors.initials: O
authors.lastname: Kukuy
authors.affiliation: Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. yonatankassel@gmail.com.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Kassel
authors.affiliation: Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Grossman.Chagai@sheba.health.gov.il.|The Rheumatology unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Grossman.Chagai@sheba.health.gov.il.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Grossman.Chagai@sheba.health.gov.il.
authors.forename: Chagai
authors.initials: C
authors.lastname: Grossman
authors.affiliation: Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Avi.Livneh@sheba.health.gov.il.|The Rheumatology unit, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Avi.Livneh@sheba.health.gov.il.|Heller Institute of Medical research, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel. Avi.Livneh@sheba.health.gov.il.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Avi.Livneh@sheba.health.gov.il.
authors.forename: Avi
authors.initials: A
authors.lastname: Livneh
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D010505:Familial Mediterranean Fever / Q000188:drug therapy / Q000235:genetics*; D005838:Genotype; D006801:Humans; D009154:Mutation; D000071198:Pyrin; D050257:Tubulin Modulators / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D050257:Tubulin Modulators; D003078:Colchicine