[Genetic diagnostics of autoinflammatory diseases]

Autoinflammatory syndromes are characterized by periodic febrile attacks in combination with increased inflammatory markers. The dysregulation of different cellular signaling pathways leads to an excessive immune response, which can in turn promote multisystemic inflammatory processes. Due to overlapping symptoms, variable expressivity and pleiotropy, a purely clinical diagnosis of autoinflammatory diseases is difficult in many cases. Because an early and definitive diagnosis can greatly improve the quality of life of many patients, molecular genetic methods have become an important part of the diagnostic process. With the development of next-generation sequencing (NGS), the genetic diagnosis of patients with autoinflammatory diseases has significantly improved. Considerable progress has not only been made in the genetic characterization of undiagnosed patients, but additionally in identifying numerous new disease-associated genes; however, the plethora of molecular genetic analytical methods makes it difficult to select the method with the highest diagnostic specificity and sensitivity. The NGS technologies have also led to a large increase in the number of identified variants, making the clinical evaluation of these variants more complex. Consensus-driven and standardized molecular diagnostic guidelines, both for the diagnostic process and for the interpretation of the obtained results, have therefore become essential.