COMMON MEFV EXON 10 MUTATIONS ANALYSIS IN EGYPTIAN PATIENTS WITH FAMILIAL MEDITERRANEAN FEVER: GENOTYPEPHENOTYPE CORRELATION

Abstract

Background: Familial Mediterranean Fever (FMF) is the prototype of a group of inherited
inflammatory disorders. FMF is an autosomal recessive condition that primarily affects population of
the Mediterranean basin. If undiagnosed effectively and treated with colchicine for life it may lead to
serious consequences in terms of renal amyloidosis and renal failure. The gene (MEFV) responsible
for this disease comprises 10 exons and 781 codons. Five found mutations, V726A, M694V, M694I,
M680I and E148Q account for 74% of FMF chromosomes from typical cases (Armenians, Arabs,
Jews, and Turks. Aim of the work: The aim of our study was to characterize the MEFV gene
mutations in exon 10 in clinicaly diagnosed patients, and to examine whether there is a correlation
between the different mutations and the clinical symptoms in the affected individuals. Subjects and
Methods: The present study has been carried out on 62 patients presenting to the Internal Medicine
and Tropical Medicine Departments of Zagazig University Hospitals and outpatient clinics of Zagazig
University hospitals from May 2007 to April 2010, and 10 healthy volunteers as a control group . We
used PCR for amplification of the region that the four common mutations in exon 10 followed by
sequencing to detect Exon 10 mutations (M694I, M694V, V726A and M680I). Results: Analysis of
exon 10 0f MEFV gene showed that 42 (67.7%) had 1 or 2 identifiable mutations. Of the 42 patients
with mutations, 17 were homozygous, 11 were compound heterozygous, and 14 had only 1
identifiable mutation. The most frequent mutation was M694I in 18 (29%) followed by V726A in 12
(19%), M694V in 8 (13%), M680I (G/C) in 6 (9.6%) and M680I (G/A) in 3 (4.8%). While 20 patients
were negative for the studied mutations. Patients carrying the M680I mutation had an earlier age of
onset (2.5 years), and had no arthritis or pleurisy. Fever was present in all patients carrying the
V726A mutation, and chest and joint pains were observed in 75% of patients carrying the M694V
mutation. The least number of attacks was present in patients carrying M680I. Complete response to
colchicine therapy was obtained in all patients carrying M680I. Conclusions: These findings
underscore the importance of performing molecular studies on all suspected FMF patients. In addition
to providing accurate diagnosis, these tests allow identification of presymptomatic genetically
affected individuals, detection of the carriers and assessment of the risk for amyloidosis in later life.
PCR technique provides a rapid, reliable, cost-effective and noninvasive test for establishing a
diagnosis of FMF in symptomatic patients and also provides a rational basis for medical and genetic
counseling of FMF patients and their families.