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J Med Genet. 2013 Jun;50(6):349-59. doi: 10.1136/jmedgenet-2013-101577. Epub 2013 Mar 27.

Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature.

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CHRU Montpellier, UM1, INSERMU844, UMAI, laboratoire de génétique, Hopital A de Villeneuve, 34295, Montpellier Cedex 15, France.


Over 15 years have passed since the discovery of the first autoinflammatory gene, MEFV, responsible for familial Mediterranean fever. The identification of another gene, TNFRSF1A, in 1999 led to the concept of autoinflammation which characterises rheumatological conditions triggered by a defective innate immunity. Substantive progress has been made since then with the identification of 18 autoinflammatory genes accounting for up to 24 disease entities showing overlapping symptoms. The accumulation of studies reporting patients with missing or excess mutations as compared with expected numbers favours the hypothesis that these diseases are distributed along a continuum ranging from monogenic to multifactorial conditions, rather than featuring only classical modes of inheritance. Moreover, the probable interactions of environmental and epigenetic factors further obscure our understanding of the mechanisms underlying the phenotypic expression of patients. This review explores the history of autoinflammatory gene discovery, discusses the nosological disparities stemming from the clinical versus pathophysiological definition of autoinflammatory diseases and summarises various inheritance patterns. This review calls for a consistent disease nomenclature and presents a reconciling hypothesis which places different sequence variants within the autoinflammatory disease continuum. Integrating these new concepts should help to facilitate communication between health professionals and promote personalised patient care.



[Indexed for MEDLINE]

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