Autoinflammatory Disorders Panel

About Autoinflammatory Disorders

Autoinflammatory disorders are genetic conditions characterized by dysregulation of the innate immune system, leading to episodes of inflammation. Unlike autoimmune disorders, they are not caused by self-reactive antibodies or T lymphocytes¹. These disorders can be classified into three main categories: Type I interferonopathies, defects affecting the inflammasome, and non-inflammasome related conditions². Type I interferonopathies have an early onset and patients typically present with multi-organ dysfunction and persistent systemic inflammation³. Inflammasome-related disorders commonly feature recurrent episodes of fever, rash, arthritis, and autoinflammation^1,2. The most common form, familial Mediterranean fever, may also include abdominal manifestations¹. Non-inflammasome related conditions lead to alternations in pathways that causes autoimmunity independent of the multiprotein inflammasome complexes, subsequently leading to vast clinical presentations⁴.

These conditions can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns, with some cases arising de novo. Causative variants include both sequence variants and copy number alterations. The pathophysiology of autoinflammatory disorders is complex. While some disorders are due to variants in in genes that play a vital role in innate immunity, other disorders are polygenic, in which disease expression may be triggered by environmental factors in genetically predisposed hosts⁵. Therefore, the diagnostic yield of this panel varies greatly based on the clinical presentation and age of onset for the affected individual⁶.

All genetic tests have limitations. Please refer to our Test Methods page for limitations relevant to this methodology.

The analytical sensitivity of the PGxome platform has been validated at >99% for single nucleotide variants, >95% for indels <49 bp, and >99% for CNV ≥3 exons in size. Sensitivity is reduced in regions with repetitive elements or paralogy.

The analytical sensitivity of the PGnome platform has been validated at >99% for sequence variants and >99% for structural variants (SV) 1kb-10Mb in size. Sensitivity is reduced in regions with repetitive elements or paralogy.

PGxome® platform: Capture and amplification based Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes and immediate flanking non-coding DNA (± 10 bp) in all available transcripts along with other non-coding regions harboring known disease-causing variants. Results are filtered to defined genes in panel. Reportable variants include both sequence variants and NGS-based detection of copy number variants (CNVs).

PGnome® platform: PCR-free Next Generation Sequencing (NGS) is used to sequence the coding regions of nearly all genes as well as intronic and intergenic regions. Detailed variant analysis and interpretation is focused on the coding exons and ± 10 bp into introns. Genomic variants outside of these coding regions are not investigated unless warranted (for example, if a gene of interest is highlighted by the provider, or if a single-hit pathogenic variant is found in a recessive gene). Results are filtered to defined genes in panel. Reportable variants include sequence variants; NGS-based detection of structural variants (SV), including copy number variants (CNVs) and inversions; and repeat expansion variants in currently available relevant genes.

Variants not meeting our quality threshold through NGS alone are confirmed with an orthogonal method, including but not limited to Sanger and array.

All variants within the analyzed genes which are classified as pathogenic, likely pathogenic, risk, or variant of uncertain significance will be reported.