title: Familial Mediterranean fever patients homozygous for E148Q variant may have milder disease.
abstract: OBJECTIVE
  Familial Mediterranean fever (FMF) results from MEFV gene mutations. E148Q is a variant of unknown significance in MEFV. We aimed to define characteristics of FMF patients homozygous for E148Q, check for other MEFV variants in a subgroup, and compare the characteristics with FMF patients carrying other mutations.
  
  
  METHODS
  Thirty FMF patients homozygous for E148Q were reviewed. MEFV variant analysis was performed with strip assay. All MEFV exons were screened by direct DNA sequencing in 14 randomly selected E148Q/E148Q patients. E148Q was also checked in 100 healthy adolescents. We compared the characteristics of FMF patients between three groups: E148Q/E148Q (n = 30), M694V/E148Q (n = 19) and exon 10/exon 10 MEFV mutations (n = 48).
  
  
  RESULTS
  Among 30 FMF patients (E148Q/E148Q), the median age at disease onset and diagnosis were 60 (12-168) and 94 (41-196) months, respectively. Fifteen (50%) patients had mild, 14 (46.7%) moderate and one (3.3%) had severe disease. Twenty-two (73.3%) patients had complete, seven (23.3%) had incomplete response to colchicine, while only one was unresponsive. The detected MEFV variants in 14 E148Q/E148Q FMF patients were as follows: R314R (n = 9; 64.3%), E474E (n = 13; 92.9%), Q476Q (n = 13; 92.9%), D510D (n = 13; 92.9%), and P588P (n = 8; 57.1%). The E148Q allele frequency was 6.5% in healthy adolescents. When compared to FMF patients with other MEFV mutations, disease onset was later, disease was less severe and the ratio of patients responding completely to colchicine was higher in E148Q/E148Q patients.
  
  
  CONCLUSIONS
  Patients homozygous for E148Q and negative for other pathogenic MEFV variants may display FMF phenotype and may experience moderate/severe disease activity, although the disease may be milder when compared to FMF patients with other mutations.
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Rezan
authors.initials: R
authors.lastname: Topaloglu
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Ezgi Deniz
authors.initials: ED
authors.lastname: Batu
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Çigdem
authors.initials: Ç
authors.lastname: Yıldız
authors.affiliation: Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Emine
authors.initials: E
authors.lastname: Korkmaz
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Seza
authors.initials: S
authors.lastname: Özen
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Nesrin
authors.initials: N
authors.lastname: Beşbaş
authors.affiliation: Department of Pediatric Nephrology and Rheumatology, Hacettepe University Faculty of Medicine, Ankara, Turkey.|Nephrogenetics Laboratory, Hacettepe University Faculty of Medicine, Ankara, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Özaltın
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D005091:Exons; D010505:Familial Mediterranean Fever / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D000071198:Pyrin / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: C000604192:MEFV protein, human; D000071198:Pyrin; D003078:Colchicine
keywords: E148Q; MEFV gene; familial Mediterranean fever; variant of unknown significance