Genotype–phenotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation-independent amyloidosis

Abstract

None of the four missense mutations is associated with a severe disease or the development of amyloidosis in Turkish FMF patients living in Turkey. The influence of unknown environmental factors and/or the presence of other genetic changes are necessary to explain the phenotypic variation of the disease and the development of amyloidosis.

The spectrum of Familial Mediterranean Fever (FMF) mutations

“…31,32 Unexpectedly though, the presence of M694V was not found to be associated with a severe form of the disease or the development of amyloidosis in an independent series from Ankara. 33,34 This group recently reported that patients with the G138 polymorphism in exon 2 were more prone to amyloidosis. 35 Other mutations at codon 694 and mutation M680I are also possibly severe ones.…”

“…23 V726A prevalence is generally higher in populations with mild disease, 3,40,42 but genotypes including this mutation may be found in patients with amyloidosis. 33,34 In one Jordanian series however, genotypes including V726A were associated with a more severe disease than those with M680I. 43 Mild phenotype or incomplete penetrance have also been described in patients with K695R or P369S.…”

“…62 Indeed, the spectrum of MEFV mutations in Armenians was similar in all countries, demonstrating that the differences in the amyloidosis rates were not exclusively due to this genetic factor. 20,21 Keeping this in mind, and the discordant results that have been described in Turks and Arabs series, 33,34,43 comparative statistics implementing possible confusing factors such as access to treatment, consanguinity, ethnicity, etc..., are necessary to definitively elucidate the question of phenotype-genotype correlation in FMF. Therefore, both clinical and genetic data have still to be taken into account for the patient care.…”

High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey

“…3,5,[9][10][11][12][13][14][15][16]20,21 The most common mutation characterized in Turks is the M694V mutation with the frequency of 30-50%. The E148Q mutation occurs at a frequency ranging from 1.4-11.4% according to some previous studies.…”

“…2,7 Gene sequence and phenotypic characteristics of FMF patients change according to geographic regions, which include people from certain ethnic origins both in Turkey and in the World. 1,2,[7][8][9][10][11][12][13][14][15][16][17] Unfortunately, there is a paucity of studies that have investigated the genotypic and phenotypic variations of FMF patients in southeast Turkey. 3 Therefore, we aimed to investigate the genotypic and phenotypic characteristics of children with FMF in southeastern Turkey.…”