Diagnostic value of array-based genotyping in autoinflammatory syndromes

Rationale: Autoinflammatory syndromes are rare immunological disorders. More
than forty distinct syndromes have been described in literature. These patients
present with episodes of recurrent fever and other symptoms, and are usually
asymptomatic between attacks. During diagnostic work-up, there is no evidence
of infection or auto-immune disease. Most syndromes have a genetic background
and are caused by specific genetic mutations in genes that cause dysregulation
in the innate immune system. Genetic testing is crucial to acquire a diagnosis
and select an appropriate treatment. Unfortunately, genetic testing is
expensive and time consuming and therefore not widely available in developing
countries. Previously, we developed an genotyping array to screen for
pathogenic mutation in primary immunodeficiency disorders (PID). Genotyping
arrays are cheap and have a rapid turn-around time and can therefore be used as
a first screening to limit the use of expensive genetic testing. Theoretically,
this technique and strategy can be applied to all diagnostic conditions. In
this research, we focus on patients suffering from an autoinflammatory disorder
and aim to investigate whether array-based genotyping approaches have the
potential to pick up genetic variants, and could be used as a first screening
tool in future for autoinflammatory patients.

Objective: The primary objective of this study is to investigate the potential
of the custom global screening array (GSA) in patients with autoinflammatory
disorders. We aim to investigate whether the GSA can pick up genetic variants
in genes known how many patients with autoinflammatory disease could
potentially be diagnosed with the use of the GSA and the genetic incidental
findings by GSA. This research is a preliminary pilot study to investigate
whether the GSA has the potential to be developed in the future into a in-vitro
diagnostic.

Study design: Single-center diagnostic accuracy cross-sectional pilot study.

Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: In this research, there will be a minimal burden
for the patients. There will be no risk associated with participation. During a
regular blood draw to monitor the disease an extra tube of blood will be drawn
from which DNA will be isolated. This research will help to add to our
knowledge about array-based genotyping in rare genetic diseases, specifically
autoinflammatory disorders. If this technique shows positive results, in the
future one can perform larger studies to investigate the diagnostic value of
array-based genotyping in autoinflammatory disorders and improve our diagnostic
approach.