Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF)

Abstract

Familial Mediterranean fever (FMF) is an autosomal recessive disease clinically characterized by recurrent short self‐limited attacks of fever accompanied by peritonitis, pleurisy, and arthritis and can lead to amyloidosis and renal failure in the longer term. It is prevalent mainly in non‐Ashkenazi Jews, Armenians, Turks, and Arabs. Due to the lack of an accurate diagnostic test, patients often experience years of attacks and invasive diagnostic procedures before the correct diagnosis is made and adequate treatment is begun. Recently, the gene responsible for FMF, denoted pyrin, has been cloned, and three disease mutations have been described (French FMF Consortium, 1997; International FMF Consortium, 1997). In the current study we assessed the spectrum of mutations in this gene in 16 unrelated families of Turkish origin. The three previously reported missense mutations (Met‐Ile at codon 680, Met‐Val at codon 694, and Val‐Ala at codon 726) accounted for 29 of the 34 disease alleles. In one patient in whom no disease mutation was identified, the clinical picture was atypical enough to raise questions regarding the diagnosis. These results imply that the origin of FMF in Turkey is heterogeneous, that molecular diagnosis of FMF is possible in the majority of cases and clinically helpful, and that delineation of the undiscovered disease mutation(s) in the remaining cases remains a high priority. Hum Mutat 11:456–460, 1998. © 1998 Wiley‐Liss, Inc.

Significance of MEFV gene R202Q polymorphism in Turkish familial Mediterranean fever patients

“…Of the known hereditary periodic fevers, FMF is the most prevalent and best characterized. It is an autosomal recessive disorder, which predominantly affects people living in or originating from areas around the Mediterranean basin, mainly Jews, Armenians, Turks and Arabs (Chen et al, 1998;Touitou et al, 1998). Mediterranean fever (MEFV) gene has already been identified as being responsible for FMF (The International FMF Consortium, 1997).…”

Clinical, laboratory and molecular characteristics of children with Familial Mediterranean Fever-associated vasculitis

“…Misdiagnosis is unlikely in these children because all had a typical history of FMF attacks and one had a strong family history. Our results probably reflect mutation spectrum of Turkish people with FMF and are consistent with those of a previous study (22).…”

“…found in 85% of the carrier chromosomes that were mainly obtained from Jewish FMF patients (10,11). Similarly, three mutations (M680I, M694V and V726A) were found in 85% of Turkish FMF patients in a recent study (22). Our unpublished data, which included 238 Turkish FMF patients, showed a similar frequency.…”

“…Thirteen others were found to have the M694V mutation on one allele. These frequencies seem not to differ from those found in a group of Turkish FMF patients that were not specified as having vasculitis in a recent study (22). More studies are needed to determine if a particular mutation or combination of mutations are associated with vasculitis in FMF.…”

Study of the Mutation M694V of Familial Mediterranean Fever in Jews

“…Since the first two main publications by the two consortia, various other studies confirmed the preponderance of the M694V mutation in north African Jews, Oriental Jews, Armenians, and Turks (Dewalle et al, 1998;Eisenberg et al, 1998;Chen et al, 1998;Shohat et al, 1999;Aksentijevich et al, 1999;Cazeneuve et al, 1999;Dodé et al, 2000). One of the other main FMF mutations, V726A (The French FMF Consortium, 1997; The International FMF Consortium, 1997), occurs relatively frequently in non-Ashkenazi Jews, Iraqi Jews, Armenians, and Turks (Chen et al, 1998;Eisenberg et al, 1998;Aksentijevich et al, 1999).…”