Susceptibility to Infection Panel

About Susceptibility to Infections

Defects in intrinsic and innate immunity are genetic disorders that increase susceptibility to specific micro-organisms in otherwise healthy individuals¹. Over 60 disorders fall into this category, including Mendelian susceptibility to mycobacterial disease (MSMD), epidermodysplasia verruciformis (HPV susceptibility), predisposition to severe viral infections, herpes simplex encephalitis (HSE), and chronic mucocutaneous candidiasis (CMC)². Individuals with MSMD are susceptible to weakly virulent mycobacteria, including the bacillus Calmette-Guerin (BCG) vaccine and non-tuberculous environmental mycobacteria^3,4. CMC presents as a persistent Candida fungal infection of the mucous membranes, scalp, skin, and/or nails due to selective T cell deficiency (IDF)⁵.

The disorders follow autosomal dominant, autosomal recessive, or X-linked inheritance patterns, with de novo variants also reported. The diagnostic yield of this panel will vary based on the clinical phenotype of the patient and the specific disorder suspected. However, for MSMD, variants in IL12RB1, IFNGR1, IL12B, and IFNGR2 account for the majority of cases⁴. Genes reported in association with CMC include IL17F, IL17RA, IL17RC, TRAF3IP2, STAT1, and MAPK8⁵.

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.