Comprehensive MEFV Variant Spectrum in Pediatric Patients with Suspected Familial Mediterranean Fever: A Whole-Gene Sequencing Study

OpenAlex Türkçe

Familial Mediterranean Fever (FMF) (OMIM #249100) is one of the most common monogenic autoinflammatory diseases and is characterized by recurrent fever attacks and inflammatory findings such as peritonitis, pleuritis, arthritis, and erysipelas-like erythema.1,2,3 The disease is particularly common in populations living in the Mediterranean basin; Türkiye is among the countries with a high prevalence of FMF. 4,5In cases that begin in childhood, early diagnosis is important for initiating appropriate treatment and preventing long-term complications.6,7 FMF is mainly associated with variants in the Mediterranean Fever (MEFV) gene, which is located on the short arm of chromosome 16 and encodes the pyrin protein.2,4 Although numerous variants have been identified in the MEFV gene, commonly observed variants such as M694V, V726A, M680I, M694I, and E148Q are detected in a significant proportion of cases.1,5 However, when examinations are performed with standard panels, no diagnostic result can be reached in some cases, suggesting that rare or out-of-panel variants, in particular, may be overlooked.1,3 In an FMF-specific study, broader next-generation sequencing (NGS)-based analysis of patients with negative or single-heterozygous results after traditional 16-variant screening identified clinically relevant variants in 34% of cases and detected previously missed MEFV variants in 54 patients.8 This indicates that traditional