Familial Mediterranean fever without MEFV mutations: a case–control study

Orphanet Journal of Rare Diseases

Avi Livneh¹  Chagai Grossman¹  Yonatan Kassel²  Olga Kukuy⁴  Corinne Herskovizh²  Ilan Ben-Zvi³ 

[1] Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;Department of Medicine F, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel;The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Ramat Gan, Israel;Institute of Nephrology and Hypertension, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

关键词: Phenotype;    Mutations;    MEFV;    FMF;    Familial Mediterranean fever;   

Others  :  1150882
DOI  :  10.1186/s13023-015-0252-7

 received in 2015-01-12, accepted in 2015-03-10,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Ben-Zvi et al.; licensee BioMed Central.

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