Mutation screening of familial Mediterranean fever in the Azeri Turkish population: Genotype-phenotype correlation and the clinical profile variability

Familial Mediterranean fever is known as a most frequent hereditary autoin-Xammatory among the autoinflammatory syndromes characterized by fever, arthritis and serosal inflammation. Clinically, the foremost severe symptom of the disease is amyloidosis, which may cause to renal failure. MEFV renal failure consists of ten exons and conservative mutations clustered in exon ten (M694V, V726A, M680I, M694I) and exon two (E148Q) are considered more common mutations within this coding region and that they are detected with a distinct frequency changes in line with ethnicity. The aim of this study was to research the spectrum of mutations in Azeri Turkish population. We evaluated the molecular test results of 82 patients and their parents from eighty families identified as having FMF clinical symptoms referred to Molecular Genetics Laboratory of the Department of Medical Genetics. Patients were referred by their physicians for MEFV mutation detection. The most frequent mutations were M694V respectively followed by M680I (G/C), V726A, M694I and E148Q mutations. A phenotypic variability was also ascertained between patients with different mutations and it must be considered within the daily management of FMF patients.

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The Frequency of Familial Mediterranean Fever Gene Mutations and the Correlations between Phenotype and Genotype in Turkish Children

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2020/v4i230145 ◽

2020 ◽

pp. 20-26

Author(s):

Hakan Erdogan ◽

Ayse Cavidan Sonkur ◽

Orhan Görükmez ◽

Ayse Erdogan ◽

Dilek Damla Saymazlar ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mutation Screening ◽

Mefv Gene ◽

Gene Mutations ◽

Retrospective Case ◽

Turkish Children ◽

Pathogenic Variants ◽

Frequent Mutations ◽

Training And Research ◽

Mediterranean Fever

Aim: Familial Mediterranian Fever is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 158 children (78 male, 80 female) diagnosed with Familial Mediterranean Fever (FMF) and to compare the phenotype-genotype correlation. Methods: In our retrospective case-control study, 158 FMF patients (78 males, 80 females) who were diagnosed with MEFV gene mutation in Bursa Yuksek Ihtisas Training and Research Hospital, Department of Pediatrics between January 2018 and June 2019 were included in the study. Mutation screening of the MEFV gene was performed for 12 mutations and the 8 most common mutations were taken into the study. Results: Abdominal pain (77.8%), fever (74%) and arthralgia (46.2%) were the most prevalent clinical features in our patients. The most frequent mutations were M694V, E148Q, V726A, M680I and P369S. In cases with M694 mutation, it was noted that the incidence of arthritis was 2.5 times, appendectomy frequency 3.1 times higher, and early diagnosis probability 3.2 times higher. The frequency of chest pain was 2.9 times higher in the M680I mutation, and the frequency of arthralgia was 2.2 times higher in the P369S mutation. Conclusion: Patient’s mutations in FMF patients are important for clinical expectations, and some mutations such as P369S are not as innocent as expected. However, reevaluation of phenotypes of mutations that are rare with more patients will be significant.

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Molecular Diagnosis Experience in Familial Mediterranean Fever: The Most Frequent Mutations in the MEFV Gene

Medical Bulletin of Haseki ◽

10.4274/haseki.42714 ◽

2018 ◽

Vol 56 (1) ◽

pp. 42-49 ◽

Cited By ~ 1

Author(s):

Ender Coşkunpınar ◽

Ayla Özvarnalı ◽

Kıvanç Çefle ◽

Ayşe Palanduz ◽

Ahmet Gül ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Molecular Diagnosis ◽

Mefv Gene ◽

Frequent Mutations ◽

Mediterranean Fever

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Fiatal felnőtt korban diagnosztizált familiáris mediterrán láz

Hematológia−Transzfuziológia ◽

10.1556/2068.2020.53.4.6 ◽

2020 ◽

Vol 53 (4) ◽

pp. 201-205

Author(s):

Henrietta Poset ◽

Judit Kárteszi ◽

Tibor Kalmár ◽

Zoltán Maróti ◽

Julianna Fekete ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Clinical Symptoms ◽

Clinical Status ◽

Molecular Genetic ◽

Mefv Gene ◽

Young Female ◽

C1 Inhibitor Deficiency ◽

First Line Therapy ◽

Hereditary Autoinflammatory Diseases ◽

Mediterranean Fever

Összefoglaló. A familiáris mediterrán láz a herediter autoinflammatorikus betegségek közé tartozik. Klinikai tüneteit döntően a savós hártyák akut gyulladása (serositis: peritonitis, pleuritis, synovitis, ritkán pericarditis, meningitis) határozza meg. A betegség hátterében a pyrin fehérjét kódoló MEFV-gén többségében autoszómális recesszív módon öröklődő mutációi állnak. Legfontosabb szövődménye az amyloidosis, amely veseelégtelenséghez vezethet. Kezelésében első vonalbeli terápiaként a colchicin szerepel. Fiatal nőbetegünket 12 éves kora óta több intézetben vizsgálták intenzív hasi fájdalommal és lázzal járó attakok miatt. A tünettan részeként hányás, hasmenés és mellkasi fájdalom jelentkezett. A gyulladásos epizódok 5–14 napig tartottak, a köztes időszakokban viszont teljesen jól volt. A rohamok alatt készült laboratóriumi vizsgálatok során leukocitózis, valamint emelkedett süllyedés és CRP mutatkozott. Intravazális hemolízisre utalt az anémia, retikulocitózis, magas Sebi, szérum szabad hemoglobin és LDH együttes megjelenése. Az EKG-én inferior és az anteroseptalis elvezetésekben átmenetileg negatív T-hullámok jelentek meg, ami pericarditis lehetőségét vetette fel. Fizikális státuszából kiemelendő a diszkrét, de progrediáló splenomegalia. Kizártuk a porphyriat, glucose-6-phosphat dehydrogenase-hiányt, PNH-t és C1-inhibitorhiányt. Az autoinflammatorikus betegség miatt elvégzett molekuláris genetikai vizsgálat az MEFV-génmutáció homozigóta formáját, a Familiáris mediterrán láz diagnózisát igazolta. Summary. The familial Mediterranean fever is one of the hereditary autoinflammatory diseases. Its clinical symptoms are mainly determined by acute inflammation of the serous membranes (serositis: peritonitis, pleurisy, synovitis, rarely, pericarditis, meningitis). The background of the disease is mostly represented by autosomal recessively inherited mutations in the MEFV gene encoding the pyrine protein. Its most important complication is amyloidosis, which can lead to renal failure. Colchicine is included in its treatment, as a first-line therapy. Our young female patient has been examined in several institutions since the age of 12 for attacks of intense abdominal pain and fever. The symptoms included vomiting, diarrhea, and chest pain. The inflammatory episodes lasted 5–14 days, but in the intervening periods she was free of symptoms. Laboratory tests performed during the inflammatory periods showed leukocytosis as well as increased ESR and CRP. Intravascular hemolysis was indicated by anemia, reticulocytosis, co-occurrence of high Sebi, serum free hemoglobin and LDH. On the ECG, transiently negative T waves appeared in the inferior and anteroseptal leads, raising the possibility of pericarditis. Of her clinical status, discrete but progressive splenomegaly should be highlighted. Porphyria, glucose-6-phosphat dehydrogenase deficiency, PNH, and C1 inhibitor deficiency were excluded during our examinations. Molecular genetic testing urged by autoinflammatory disease confirmed a homozygous form of the MEFV gene mutation and established the diagnosis of familial Mediterranean fever.

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