Genetics of Autoinflammatory Diseases


Autoinflammatory diseases (AIDs) are a genetically heterogeneous group of diseases caused by pathogenic variants of genes encoding proteins with a crucial role in the regulation of the inflammatory response. In the pathogenesis of AIDs, the genetic background is triggered by environmental factors through the modulation of the innate immune system. Monogenic AIDs are characterised by Mendelian inheritance and are caused by highly penetrant genetic variants in single genes. The monogenic AIDs are familial Mediterranean fever, mevalonate kinase deficiency, tumour necrosis factor receptor‐associated periodic syndrome, cryopyrin‐associated periodic syndromes, deficiency of interleukin‐1 receptor antagonist, Blau syndrome, pyogenic arthritis, pyoderma gangrenosum and acne syndrome and Majeed syndrome.

Key Concepts

  • Autoinflammatory diseases are caused by pathogenic variants of genes encoding proteins with a crucial role in the regulation of the inflammatory response.
  • Monogenic AID are characterised by Mendelian inheritance and are caused by highly penetrant genetic variants in single genes.
  • The diagnosis of AIDs is often difficult, because of the rarity of the diseases and aspecifical clinical phenotype.
  • FMF is inherited as autosomal recessive disease, although a significant proportion of heterozygous individuals also express the phenotype.
  • In the areas near the Mediterranean Sea, the carrier rate for MEFV is high, with peaks of 1/3–1/6, representing the highest carrier rates reported for an autosomal recessive disorder.
  • MEFV carriers probably had a selective advantage in the resistance to an endemic pathogen.
  • Genomic data combined with clinical information may help diagnosis for those patients with intermediate phenotype.

Keywords: autoinflammatory diseases (AID); hereditary periodic fevers; familial Mediterranean fever; mevalonate‐kinase deficiency; TRAPS; cryopyrinopaties; inflammasome


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Further Reading

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Martorana, Davide, Bonatti, Francesco, Adorni, Alessia, Mozzoni, Paola, Uliana, Vera, and Percesepe, Antonio(Jun 2018) Genetics of Autoinflammatory Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028109]