title: The carrier rate and spectrum of MEFV gene mutations in central and southeastern European populations.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) is an autosomal-recessive disorder caused by mutations in MEFV gene. Eastern Mediterranean populations have the highest number of carriers, whereas western Mediterranean populations are less frequently affected. The aim of this study was to determine the carrier rate and spectrum of MEFV gene mutations in apparently healthy populations and in suspected FMF patients from central and southeastern European (CSEE) countries.
  
  
  METHODS
  We screened 507 apparently healthy persons from 5 CSEE countries. Exons 2 and 10 of the MEFV gene were PCR amplified and subsequently sequenced with ABI prism310 genetic analyser. Six most common mutations in the MEFV gene were tested: V726A, K695R, M694V, M694I, M680I in exon 10, and E148Q in exon 2. In suspected FMF patients we screened all MEFV exons in selected cases.
  
  
  RESULTS
  The overall carrier frequency of all MEFV mutations was higher than expected (9.3%). In the whole cohort we did not find any apparently healthy persons with two mutations. Heterozygous mutations were found in apparently healthy subjects from different CSEE countries as follows: Macedonia 16%, Serbia 11%, Bosnia and Herzegovina 8%, Slovenia 6% and Hungary 5%. The most common mutation in healthy controls was K695R, appearing in 40% of mutated alleles. The most common mutation in suspected FMF patients was M694V, followed by K695R.
  
  
  CONCLUSIONS
  We found a higher than expected carrier rate of MEFV gene mutations in populations from CSEE countries. It is interesting to note that 40% of detected carriers carry the K695R mutation.
authors.affiliation: Unit for Special Laboratory Diagnostics, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
authors.forename: Maruša
authors.initials: M
authors.lastname: Debeljak
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center; and Faculty of Medicine, University of Ljubljana, Slovenia.
authors.forename: Nataša
authors.initials: N
authors.lastname: Toplak
authors.affiliation: University Children Hospital, Medical Faculty, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia.
authors.forename: Nora
authors.initials: N
authors.lastname: Abazi
authors.affiliation: Unit of Paediatric Rheumatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Szabados
authors.affiliation: Children's Hospital University, Clinical Center, Sarajevo, Bosnia and Herzegovina.
authors.forename: Velma
authors.initials: V
authors.lastname: Mulaosmanović
authors.affiliation: Faculty of Medicine, University of Niš, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Radović
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center, Ljubljana, Slovenia.
authors.forename: Daša
authors.initials: D
authors.lastname: Perko
authors.affiliation: Faculty of Medicine, University of Niš, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Vojnović
authors.affiliation: Unit of Paediatric Rheumatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: Tamas
authors.initials: T
authors.lastname: Constantin
authors.affiliation: University Children Hospital, Medical Faculty, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia.
authors.forename: Dafina
authors.initials: D
authors.lastname: Kuzmanovska
authors.affiliation: Department of Allergology, Rheumatology and Clinical Immunology, University Children's Hospital, University Medical Center; and Faculty of Medicine, University of Ljubljana, Slovenia. tadej.avcin@kclj.si.
authors.forename: Tadej
authors.initials: T
authors.lastname: Avčin
mesh_terms: D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D005091:Exons; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D015995:Prevalence; D000071198:Pyrin; D012307:Risk Factors
chemical_list: D003598:Cytoskeletal Proteins; D005819:Genetic Markers; C000604192:MEFV protein, human; D000071198:Pyrin