Current practices for the genetic diagnosis of autoinflammatory diseases: results of a European Molecular Genetics Quality Network Survey

Abstract

Monogenic autoinflammatory disorders (AIDs) are rare diseases caused by variants in genes regulating the innate immune system. The identification of the first four genes responsible for the prototype group of hereditary recurrent fevers prompted the development of genetic diagnosis, followed by external quality assessment and guidelines for the interpretation of sequence variants in these diseases. Recent changes in the diagnosis of genetic diseases, namely the implementation of next-generation sequencing (NGS), lead to discovery of the new genes associated with at least 40 novel AIDs, which revolutionized patient care and prognosis. However, these rapid advances resulted in nonstandardized molecular strategies that can influence genetic diagnosis and reporting of results. In order to assess factors, which may have an impact on performance and quality of results in the NGS era, we carried out an online survey among member laboratories of the European Molecular Genetics Quality Network, which highlighted different strategies being used and identified pitfalls that deserve discussion and improvement.

Fig. 1

Prerequisites for the genetic diagnosis of AID. On the left: Administrative prerequisites. The three responses “Other” were out of the scope of this question (see text) and are not mentioned here. On the right: Medical prerequisites. AID autoinflammatory disorder

Fig. 2

Testing of asymptomatic individuals. A nonuniform approach to test request and reporting procedures was found among the 23 participating laboratories

Fig. 3

Technical approach used. On the left: DNA analysis strategy. On the right: Validation of DNA results strategy. The total number of responses exceeds the number of participants because it is a multichoice question