Frequency of mutations in Mediterranean fever gene, with gender and genotype–phenotype correlations in a Turkish population

Abstract

Familial Mediterranean fever (FMF) is the most common hereditary inflammatory periodic disease, characterized by recurrent episodes of fever, abdominal pain, synovitis and pleurisy. The aim of this study was to determine the frequency and distribution of Mediterranean fever (MEFV) gene mutations and to investigate the clinical characteristics and genotype-phenotype correlation in patients with FMF in Aydin, a province in western Anatolia, Turkey. Therefore, we retrospectively analysed MEFV gene mutations in 383 patients with suspected FMF and the clinical features of 327 among them. The MEFV gene mutations were investigated using the reverse dot-blot hybridization technique. We detected 26 different genotypes and 11 different mutations. The most common mutations in our cohort were p.M694V (41.15%), p.E148Q (20.35%), p.M680I(G/C) (12.39%) and p.R761H (9.73%). Abdominal pain (86.2%), fever (80.7%), arthralgia (57.2%), vomiting (36.1%), arthritis (34.6%), fatigue (31.5%), anorexia (22.9%) and chest pain (19.0%) were the most prevalent clinical features in our patients. This is the first study from Aydin in which the distribution of MEFV gene mutations and clinical features were evaluated in patients with FMF. We found that the most common mutation was p.M694V in our region, while the frequency of the p.R761H mutation was higher compared to other regions of Turkey with respect to extracted data from previous similar studies. Presented results supported the clinical findings in the literature that the homozygous p.M694V and compound heterozygous genotype were associated with more severe courses in FMF patients.

Association between sequence variations of the Mediterranean fever gene and the risk of migraine: a case–control study

“…During FMF attacks, neurological complications are also reported. In various studies, the prevalence of headache has been reported as approximately 5% to 20% among FMF patients 7,23,25,26. Gedalia et al34 reported that of 101 patients, ten experienced headaches during FMF attacks.…”

“…In addition, FMF and migraine both have recurrent, periodic, painful symptoms. In the literature, a number of clinical observations have long suggested a possible relationship between headache and FMF 7,22–26. Furthermore, a clinical study reported that the prevalence of migraine in patients with FMF was 29.1% in the Turkish population 6.…”

Mutaciones en el gen MEFV y evolución clínica en pacientes pediátricos con púrpura de Schönlein-Henoch

“…11 En otro estudio, las mutaciones más comunes observadas en el gen MEFV fueron p.M694V (41,15%), p.E148Q (20,35%), p.M680I(G/C) (12,39%) y p.R761H (9,73%) en la población turca. 12 Las mutaciones en el gen MEFV codifican la proteína pirina, que juega un papel importante en las vías inflamatorias al disminuir la inflamación, especialmente en los neutrófilos; por lo tanto, la proteína mutada puede causar inflamación incontrolable y favorecer la aparición de PSH y de otras variedades de vasculitis. 12 La vasculitis puede ser una manifestación clínica de la FMF con una prevalencia familiar más alta.…”

“…12 Las mutaciones en el gen MEFV codifican la proteína pirina, que juega un papel importante en las vías inflamatorias al disminuir la inflamación, especialmente en los neutrófilos; por lo tanto, la proteína mutada puede causar inflamación incontrolable y favorecer la aparición de PSH y de otras variedades de vasculitis. 12 La vasculitis puede ser una manifestación clínica de la FMF con una prevalencia familiar más alta. En pacientes con FMF, las mutaciones en el gen MEFV pueden actuar como factor de susceptibilidad genética para la vasculitis.…”

“…13 Los portadores de la mutación pueden tener mayores respuestas inflamatorias con síntomas clínicos severos; además, el análisis ha indicado que la depuración anormal de los inmunocomplejos y la desregulación de la respuesta inflamatoria se debieron a locus genéticos defectuosos. 12 Nuestro objetivo fue determinar la frecuencia de mutaciones en el gen MEFV en pacientes de entre 2 y 11 años con diagnóstico de púrpura de Schönlein-Henoch y evaluar el efecto de la presencia de mutaciones en el gen MEFV en su pronóstico.…”