American Journal of Pharmacogenomics

, Volume 4, Issue 2, pp 109–118 | Cite as

Identifying Mutations in Autoinflammatory Diseases

Towards Novel Genetic Tests and Therapies?
  • Isabelle Touitou
  • Cécile Notarnicola
  • Sylvie Grandemange
Molecular Diagnostics


Autoinflammatory diseases are defined as illnesses caused by primary dysfunction of the innate immune system. This new concept includes a broad number of disorders, but the spotlight has been focused for the past two years on periodic fevers (familial Mediterranean fever [FMF]; mevalonate kinase deficiency [MVK]; tumor necrosis factor [TNF] receptor-associated periodic syndrome [TRAPS]; cryopyrin-associated periodic syndrome [CAPS]), Crohn’s disease and Blau syndrome, thanks to the recent understanding of their molecular basis. Indeed, until recently, these conditions were defined only by phenotypical features, the main ones being recurrent attacks of fever, abdominal pain, arthritis, and cutaneous signs, which sometimes overlap, obscuring diagnosis. The search for distinguishing signs such as periorbital edema in TRAPS, and the use of specific functional tests where available, are valuable. Needless to say, molecular screening of the causative genes has dramatically improved patient quality-of-life by providing early and accurate diagnosis, subsequently allowing for the appropriate treatment. Some patients, however, remain hard to manage despite the advent of new genetic tests, and/or due to the lack of effective treatment.

The original clinical link between the aforementioned diseases can now be confirmed by a molecular one, following the exciting discovery that most of the altered proteins are related to the death domain fold (DDF) superfamily involved in inflammation and apoptosis. These molecules mediate the regulation of nuclear factor-kappa B (NF-κB) activation, cell apoptosis, and interleukin-1β secretion through cross-regulated and, sometimes, common signaling pathways. Knowledge of the defective step in autoinflammation has already led to the elucidation of the mechanisms of action of existing drugs and may allow the development of new therapies.



The authors want to thank E. Aganna, D. Cattan, L. Cuisset, C. Dodé, S. Houten, M. McDermott, I. Koné-Paut, A. Simon, and H. Waterham for fruitful exchanges. ## This work was supported by the Centre National de la Recherche Scientifique (CNRS), the Centre Hospitalier-Universitaire (CHU) de Montpellier, and the European Community (5th framework). The authors have no conflicts of interest that are directly relevant to the content of this review.


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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Isabelle Touitou
    • 1
  • Cécile Notarnicola
    • 1
  • Sylvie Grandemange
    • 1
  1. 1.Laboratoire de Génétique Moléculaire et ChromosomiqueHôpital Arnaud de VilleneuveMontpellier Cedex 5France

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