Predictive Clinical and Biological Criteria for Gene Panel Positivity in Suspected Inherited Autoinflammatory Diseases: Insights from a Case–Control Study

Abstract

In order to assess the clinical and biological criteria that predict gene panel positivity in patients with a suspected inherited genetic autoinflammatory disease, we conducted a case–control study. These new selection criteria could replace the national multidisciplinary staff approval before performing genetic testing that has been required since 2019. The study involved 119 positive gene panels matched by panel sizes to 119 randomly selected negative gene panels. The patients were referred to our laboratory for genetic testing between June 2012, and March 2023. The clinical and biological criteria were extracted from a prospectively filled database. We focused our evaluation on accuracy and the positive predictive value. Neonatal symptom onset and deafness had the highest accuracies among all criteria associated with the positivity panel, with 92.9% (88.6; 96.0) and 92.6% (88.5; 95.6), respectively. However, it is important to note that the associated Positive Predictive Values (PPVs) cannot exceed 50%. Despite finding a statistical association between clinical and biological criteria and panel positivity, the predictive values of these criteria were not sufficient to recommend Next-Generation Sequencing (NGS) gene panel testing without the national multidisciplinary staff evaluation.

Keywords

• hereditary recurrent fevers
• high-throughput sequencing
• inflammation
• predictive value of tests
• retrospective studies