The Spectrum of MEFV Gene Mutations and Genotypes in the Middle Northern Region of Turkey

Objective: Familial Mediterranean fever (FMF) is a common, inherited, autosomal recessive inflammatory disease in children. The diagnosis of FMF is based on clinical features and positive family history supported with genetic testing. This study aimed to determine the frequency and distribution of Mediterranean fever (MEFV) gene alterations of a city in Northern Anatolia.

Materials and methods: We evaluated MEFV gene mutations in 374 children preliminary diagnosed as FMF by a commercial kit based on real-time polymerase chain reaction technique in a one-year period, and screened 12 mutations.

Results: At least one mutation was detected in 213 patients (57%) and 38 genotypes with 11 distinct mutations.A total of 137 (64. 3%) of mutation-positive children were heterozygous, 45 (21. 1%) were compound heterozygous, and 2 (0.9%) were complex heterozygous; and 14 (6.4%) patients were homozygous, 6 (2.8%) were compound homozygous, and 3 (1.4%) were complex homozygous. With a frequency of 50.1%, R202Q was the most common mutation. Also, R202Q/M694V was the most common compound heterozygous genotype. In 43 alleles, R202Q-M694V mutations were found to be in linkage disequilibrium. In our cohort, M694V, E148Q, V726A, and M680I (G/C) were other common mutations; whereas F479L, A744S, K695R, P369S, M694I, and R761H were the rare mutations. None of our patients had M680I (G/A) mutation.

Conclusion: We determined the most common MEFV alteration prevalence in children of our region for the first time. The high R202Q mutation and linkage disequilibrium (LD) rates were the remarkable results of this study.