Screening for Familial Mediterranean Fever M694V and V726A Mutations in the Greek Population

Abstract

Familial Mediterranean Fever (FMF) is an autosomal recessive genetic disease that primarily affects populations surrounding the Mediterranean basin. FMF patients suffer from recurrent episodes of fever accompanied by abdominal pain, pleuritis, and arthritis. Missense mutations in the gene for FMF (MEFV) have been shown to be responsible for the disease, while more than 70 mutations have been identified to date. The aim of the present study was to determine the carrier rates of two of the most common MEFV mutations, M694V and V726A, in the general Greek population. A cohort of 220 healthy and unrelated individuals of Greek descent was screened for the two MEFV mutations using the Amplification Refractory Mutation System. Our results showed that none of the healthy individuals tested were carriers of any of the two mutations. In conclusion, our study independently confirms that the carrier rate for the MEFV mutations M694V and V726A is extremely low in the general Greek population.

Lack of clear and univocal genotype‐phenotype correlation in familial Mediterranean fever patients: A systematic review

“…Conversely, in Greek population the carrier rate for the MEFV mutations V726A is extremely low . Although V726A is identified in populations with mild disease, a homozygous and compound heterozygous (V726A/E148Q) genotype have been also found in patients with more severe disease than those with M680I, also showing pericarditis and amyloidosis . Thus, authors highlighted the need to prescribe colchicine to patients carrying complex allele …”

“…87,88 On the other hand, the existence of a "non classic" autosomal recessive inheritance as well as of an "atypical" dominant autosomal inheritance in the FMF can not be excluded. 81 Another explanation of this phenomenon could be provided by the digenic inheritance, occurring when the interaction of 2 different genes contributes to the expression of a phenotype. Thus, it could be possible that patients carrying only one FMF mutation may produce a disease phenotype whether they are also carrying of a mutation in a gene involved in the onset of an other autoinflammatory disease.…”

“…Therefore, when only one mutation exists, the diagnosis can not be ascertained or excluded . On the other hand, the existence of a “non classic” autosomal recessive inheritance as well as of an “atypical” dominant autosomal inheritance in the FMF can not be excluded …”

“…80 Although V726A is identified in populations with mild disease, a homozygous and compound heterozygous (V726A/E148Q) genotype have been also found in patients with more severe disease than those with M680I, also showing pericarditis and amyloidosis. 81 Thus, authors highlighted the need to prescribe colchicine to patients carrying complex allele. 82 With the exception of Syrian 56 and Turkish populations 15,17,18,20,78,83,84 , R761H mutation is not frequently reported in Mediterranean populations.…”

Γονοτύπηση Με Αλληλούχιση Νέας Γενιάς Ασθενών Με Οικογενή Μεσογειακό Πυρετό Και Μακροχρόνια Παρακολούθηση Της Πορείας Της Νόσου Με Σύγχρονες Μεθόδους

“…Ακόµη και µελέτες µε πλήρη µοριακή ανάλυση του MEFV γονιδίου, συχνά αδυνατούν να ανιχνεύσουν και τη δεύτερη µετάλλαξη στο σύνολο των ασθενών Βέβαια, όταν ανευρίσκεται µία µετάλλαξη η διάγνωση του νοσήµατος δεν µπορεί να αποκλειστεί. Από την άλλη πλευρά, η ύπαρξη ενός «µη κλασικού» αυτοσωµικού υπολειπόµενου προτύπου κληρονοµικότητας, καθώς επίσης και ενός «άτυπου» αυτοσωµικού επικρατούς προτύπου κληρονοµικότητας στον ΟΜΠ δεν µπορεί να αποκλειστεί 294. Οι πιο συχνές µεταλλάξεις που ανιχνεύθηκαν στους ασθενείς της µελέτης ήταν η M694V και η Μ680Ι, µε ποσοστά 55.3% και 29.8% αντίστοιχα.…”