title: Comprehensive analysis of a large-scale screen for MEFV gene mutations: do they truly provide a "heterozygote advantage" in Turkey?
abstract: Familial Mediterranean fever (FMF) is a hereditary autoinflammatory disorder characterized by episodes of inflammation in the absence of high-titer autoantibodies or antigen-specific T cells. The Mediterranean fever (MEFV) gene located on chromosome 16p13.3, which encodes the 781-amino-acid protein pyrin, is the causative gene for this monogenic Mendelian disease. This study presents the molecular analysis of an MEFV gene mutation screen of 5518 Turkish individuals with clinical diagnoses of FMF. Patients were genetically diagnosed using the FMF StripAssay and DNA sequencing analysis. Contrary to the results achieved by the FMF StripAssay, DNA sequencing analysis identified large-scale coding and noncoding novel sequence variants, together with a significant group (76%) of individuals who were receiving colchicine and had a single heterozygous mutation, despite the recessive inheritance of FMF. In conclusion, sequence analysis, unlike other routine laboratory techniques, may enable screening for a broad range of nucleotide variations and may prevent less common, population-restricted, novel sequence variants from being overlooked.
authors.affiliation: Molecular Medicine Laboratory, Children's Hospital, School of Medicine, Ege University, Bornova, Izmir, Turkey. afigberdeli@yahoo.com
authors.forename: Afig
authors.initials: A
authors.lastname: Berdeli
authors.forename: Sevgi
authors.initials: S
authors.lastname: Mir
authors.forename: Sinem
authors.initials: S
authors.lastname: Nalbantoglu
authors.forename: Necil
authors.initials: N
authors.lastname: Kutukculer
authors.forename: Betül
authors.initials: B
authors.lastname: Sozeri
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Kabasakal
authors.forename: Sirri
authors.initials: S
authors.lastname: Cam
authors.forename: Mustafa
authors.initials: M
authors.lastname: Solak
mesh_terms: D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods*; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D009693:Nucleic Acid Hybridization / Q000379:methods; D000071198:Pyrin; D017422:Sequence Analysis, DNA / Q000379:methods; D014421:Turkey
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin