Rheumatology International

, Volume 30, Issue 5, pp 633–636 | Cite as

MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA

  • Efrat DaganEmail author
  • Ruth Gershoni-Baruch
  • Ihab Khatib
  • Adi Mori
  • Riva Brik
Original Article


PFAPA is a periodic fever disease, of unknown etiology, characterized by aphthous stomatitis, pharyngitis and cervical adenitis. To inquire whether genes implicated in other auto-inflammatory diseases might be involved in its pathogenesis, predominant mutations in the genes causing familial Mediterranean fever, TNF receptor-associated periodic fever syndrome, Crohn’s disease and Muckel–Wells syndrome were analyzed in PFAPA patients. Patients (n = 57) with PFAPA, according to previously published criteria were recruited, at the Meyer Children Hospital during 2006–2007. Clinical information was complemented during physicians–parents encounter. Predominant mutations in MEFV, TNF1rA, CARD15/NOD2 and NLRP3 genes were tested. Mean age at diagnosis was 30.64 ± 16.4 months. Boys (n = 33; 58%) were diagnosed earlier than girls (n = 21; 42%) at 26.18 ± 13.83 and 36.41 ± 18.32 months, respectively (P = 0.05). Fifteen patients (27%) carried an MEFV mutation; two patients (3.6%) a CARD15 mutation, one patient (1.8%) a variance in TNF1rA and another had both an MEFV and a CARD15 mutation. Clinical symptoms were equally manifested in carriers and non-carriers. The high carrier rate of MEFV mutations in our PFAPA cases compares well with that of the general population in Israel. It is debated whether MEFV mutations, when mediated by the presence of additional modifiers, may expose a transient fever condition, namely PFAPA.


PFAPA syndrome Auto-inflammatory disease MEFV gene TNF1rA gene CARD15/NOD2 gene NLRP3 gene 


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Efrat Dagan
    • 1
    • 2
    Email author
  • Ruth Gershoni-Baruch
    • 1
    • 3
  • Ihab Khatib
    • 4
  • Adi Mori
    • 1
  • Riva Brik
    • 3
    • 4
  1. 1.Institute of Human GeneticsRambam Health Care CampusHaifaIsrael
  2. 2.Department of Nursing, Faculty of Social Welfare and Health SciencesUniversity of HaifaHaifaIsrael
  3. 3.The Ruth and Bruce Rappaport Faculty of MedicineTechnion-Institute of TechnologyHaifaIsrael
  4. 4.Department of Pediatrics and Pediatric Rheumatology Service, Meyer Children’s Hospital of HaifaRambam Health Care CampusHaifaIsrael

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