title: MEFV gene mutations in Turkish children with juvenile idiopathic arthritis.
abstract: Mutations of the Mediterranean fever (MEFV) gene, which encodes pyrin protein, leads to familial Mediterranean fever (FMF) and a connection between MEFV mutations and rheumatic diseases has been suggested. The aim of this study was to explore the frequency and clinical significance of MEFV mutations in children with juvenile idiopathic arthritis (JIA). In this study, children with JIA, who had no typical symptoms of FMF, were screened for the mutations in exons 2 and 10 of the MEFV gene by direct sequencing. A total of 96 children, 56 girls (58.3%), with a median age of 11 years (2-18 years) were included. Patients were classified according to JIA subgroups as oligoarthritis in 43 (44.8%), rheumatoid factor-negative polyarthritis in 22 (22.9%), rheumatoid factor-positive polyarthritis in 2 (2.1%), systemic arthritis in 12 (12.5%) patients, enthesitis-related arthritis in 16 (16.7%), and psoriatic arthritis 1 (1.04%). A total of 31 children (32.3%) had MEFV mutations: 25 heterozygous, 2 homozygous, and 4 compound heterozygous. There were 22 (11.4%) exon 10 mutations (M694V, R761H, K695R, V726A, R653H) and 15 (7.8%) exon 2 mutations (E148Q, G304R, E148V, T267I). The allele frequencies of MEFV mutations were found to be 19.27%, which is higher than the general population [p = 0.03, (odds ratio (OR):1.93, 95% confidence interval (CI): 1.09-3.41)]. MEFV mutation carrier rates were significantly higher in antinuclear antibody (ANA) negative than in ANA positive patients [p = 0.01, (OR: 0.25, 95% CI: 0.085-0.74)] and in males than in females [p = 0.001, (OR: 0.197, 95% CI: 0.078-0.495)]. Also, there was a statistically significant difference between the MEFV mutation carrier rates and the subgroups of JIA (p = 0.005).
  
  
  CONCLUSIONS
  These findings suggest that mutations of the MEFV gene may be responsible for rheumatic diseases other than FMF, and patients with JIA especially males, ANA negatives, and ERA subgroups should be screened for MEFV gene mutations in countries where FMF is frequent.
authors.affiliation: Pediatric Nephrology and Rheumatology, Akdeniz University, School of Medicine, 07070, Antalya, Turkey. elif_comak@hotmail.com
authors.forename: Elif
authors.initials: E
authors.lastname: Comak
authors.forename: Cagla Serpil
authors.initials: CS
authors.lastname: Dogan
authors.forename: Sema
authors.initials: S
authors.lastname: Akman
authors.forename: Mustafa
authors.initials: M
authors.lastname: Koyun
authors.forename: Arife Uslu
authors.initials: AU
authors.lastname: Gokceoglu
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Keser
mesh_terms: D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000032:analysis*; D001171:Arthritis, Juvenile / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000032:analysis*; D006801:Humans; D008297:Male; D009154:Mutation; D000071198:Pyrin; D012217:Rheumatoid Factor / Q000032:analysis*; D017422:Sequence Analysis, DNA; D014421:Turkey / Q000453:epidemiology
chemical_list: D000974:Antibodies, Antinuclear; D003598:Cytoskeletal Proteins; D015796:HLA-B27 Antigen; C000604192:MEFV protein, human; D000071198:Pyrin; D012217:Rheumatoid Factor