MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA
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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.
KeywordsPFAPA syndrome Auto-inflammatory disease MEFV gene TNF1rA gene CARD15/NOD2 gene NLRP3 gene
- 3.Karban A, Atia O, Leitersdorf E, Shahbari A, Sbeit W, Ackerman Z, Mualem R, Levine A, Nesher S, Safadi R, Eliakim R (2005) The relation between NOD2/CARD15 mutations and the prevalence and phenotypic heterogeneity of Crohn’s disease: lessons from the Israeli Arab Crohn’s disease cohort. Dig Dis Sci 50:1692–1697. doi: 10.1007/s10620-005-2917-x CrossRefPubMedGoogle Scholar
- 11.Gershoni-Baruch R, Kepten I, Shinawi M, Brik R (1999) Direct detection of common mutations in the familial Mediterranean fever gene (MEFV) using naturally occurring and primer mediated restriction fragment analysis. Mutation in brief no. 257. Online. Hum Mutat 14:91. doi: 10.1002/(SICI)1098-1004(1999)14:1<91::AID-HUMU22>3.0.CO;2-8 CrossRefPubMedGoogle Scholar
- 15.Hull KM, Drewe E, Aksentijevich I, Singh HK, Wong K, McDermott EM, Dean J, Powell RJ, Kastner DL (2002) The TNF receptor-associated periodic syndrome (TRAPS): emerging concepts of an autoinflammatory disorder. Medicine (Baltimore) 81:349–368. doi: 10.1097/00005792-200209000-00002 CrossRefGoogle Scholar