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A monoallelic double mutation as a cause for TNF receptor-associated periodic fever syndrome

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Abstract

Hereditary periodic fever syndromes (HPFSs) are a subset of human autoinflammatory diseases characterized by periodic episodes of fever and signs of inflammation with or without involvement of inner organs. In this paper, we report phenotypic features of an index patient and affected family members that present a previously not described mutation type in the TNFRSF1A gene. The phenotype of a HPFS of affected family members was shown to be associated with two monoallelic mutations in TNFRSF1A. Primarily, the index patient was clinically diagnosed as being affected by familial Mediterranean fever (FMF). However, with molecular genetic analyses, it could be shown that the patient was in fact affected by tumor necrosis factor receptor-associated periodic syndrome, which requires a different therapy when compared with FMF. Thus, molecular genetic analyses of currently known disease loci enable the most precise diagnosis presently available and are consequently the basis for the most effective therapeutic intervention.

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References

  1. Timmann C, Schumacher J, Lamprecht P, Sudeck H, Horstmann R (2004) Genetisch bedingte Fiebersyndrome. Dtsch Arztebl 101(48):A3262–A3269

    Google Scholar 

  2. Gattorno M, Federici S, Pelagatti MA, Caorsi R, Brisca G, Malattia C, Martini A (2008) Diagnosis and management of autoinflammatory diseases in childhood. J Clin Immunol 28:73–83. doi:10.1007/s10875-008-9178-3

    Article  Google Scholar 

  3. Pras E, Aksentijevich I, Gruberg L, Balow JE Jr, Prosen L, Dean M, Steinberg AD, Pras M, Kastner DL (1992) Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16. N Engl J Med 326:1509–1513

    CAS  PubMed  Google Scholar 

  4. Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJ, Waterham HR (2001) Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet 9:253–259. doi:10.1038/sj.ejhg.5200595

    Article  CAS  PubMed  Google Scholar 

  5. Galon J, Aksentijevich I, McDermott MF, O’Shea JJ, Kastner DL (2000) TNFRSF1A mutations and autoinflammatory syndromes. Curr Opin Immunol 12:479–486. doi:10.1016/S0952-7915(00)00124-2

    Article  CAS  PubMed  Google Scholar 

  6. 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

    Article  CAS  Google Scholar 

  7. McDermott MF, Aksentijevich I, Galon J, McDermott EM, Ogunkolade BW, Centola M, Mansfield E, Gadina M, Karenko L, Pettersson T, McCarthy J, Frucht DM, Aringer M, Torosyan Y, Teppo AM, Wilson M, Karaarslan HM, Wan Y, Todd I, Wood G, Schlimgen R, Kumarajeewa TR, Cooper SM, Vella JP, Amos CI, Mulley J, Quane KA, Molloy MG, Ranki A, Powell RJ, Hitman GA, O’Shea JJ, Kastner DL (1999) Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell 97:133–144. doi:10.1016/S0092-8674(00)80721-7

    Article  CAS  PubMed  Google Scholar 

  8. Yao Q, Furst DE (2008) Autoinflammatory diseases: an update of clinical and genetic aspects. Rheumatology 47:946–951. doi:10.1093/rheumatology/ken118

    Article  CAS  PubMed  Google Scholar 

  9. The International FMF Consortium (1997) Ancient missense mutations in a new member of the RoRet gene family are likely to cause familial Mediterranean fever. Cell 90:797–807. doi:10.1016/S0092-8674(00)80539-5

    Article  Google Scholar 

  10. Aksentijevich I, Torosyan Y, Samuels J, Centola M, Pras E, Chae JJ, Oddoux C, Wood G, Azzaro MP, Palumbo G, Giustolisi R, Pras M, Ostrer H, Kastner DL (1999) Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population. Am J Hum Genet 64:949–962. doi:10.1086/302327

    Article  CAS  PubMed  Google Scholar 

  11. Cuisset L, Drenth JPH, Simon A, Vincent MF, van der Velde Visser S, Van der Meer JWM, Grateau G, Delpech M, International Hyper-IgD Study Group (2001) Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet 9:260–266. doi:10.1038/sj.ejhg.5200614

    Article  CAS  PubMed  Google Scholar 

  12. Hawle H, Winckelmann G, Kortsik CSF (1989) Familial Mediterranean fever in a German family. Dtsch Med Wochenschr 114:665–668. doi:10.1055/s-2008-1066652

    Article  CAS  PubMed  Google Scholar 

  13. Kimberley FC, Lobito AA, Siegel RM, Screaton GR (2007) Falling into TRAPS—receptor misfolding in the TNF receptor 1-associated periodic fever syndrome. Arthritis Res Ther 9:217. doi:10.1186/ar2197

    Article  PubMed  Google Scholar 

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Acknowledgments

Investigation of probands was performed according to the principles of the World Medical Association Declaration of Helsinki (WMA, General Assembly, 2004). We thank Andrea Rathmann-Schmitz for her assistance in preparing the manuscript for publication.

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Correspondence to Daniela Steinberger.

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Trübenbach, J., Wildhardt, G., Niebel, J. et al. A monoallelic double mutation as a cause for TNF receptor-associated periodic fever syndrome. Rheumatol Int 30, 805–809 (2010). https://doi.org/10.1007/s00296-009-0996-2

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  • DOI: https://doi.org/10.1007/s00296-009-0996-2

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