Cellular and Humoral Immunodeficiency Panel

About Cellular and Humoral Immunodeficiency

Cellular and humoral immunodeficiencies comprise over 50 disorders affecting T cell development or function, categorized as either severe combined immunodeficiencies (SCID) or combined immunodeficiencies (CID)^1,2. SCID represents life-threatening disorders with absence or low presence of T cells and no or low T cell function with an estimated incidence of approximately 1 in 40,000 to 100,000^3-5. SCID is typically classified into four different groups based on the absence of B and natural killer cells^3,4. SCID is further subdivided based on the number and function of T cells, with “typical” SCID having low or no T cells with no or very low T cell function and “leaky” SCID where T cell counts are higher with low or moderate T cell function⁴. A notable SCID variant is Omenn syndrome (OS) which has significantly decreased levels of B cells and elevated levels of T cells with impaired function that leads to the distinct inflammatory phenotype seen in patients with OS^4,6. CID generally present with milder manifestations than SCID that typically occur within the first two years of life and do not display full penetrance¹. These disorders can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns, with most cases lacking family history^2,5. Causative variants include sequence changes and copy number variations affecting genes crucial for immune system development. The diagnostic yield of this panel varies by phenotype and the B and natural killer cell status of the patient.

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

Coverage for IKBKG is limited due to paralogy associated with the pseudogene, IKBKGP1. NGS is not able to cover exons 3-10, including the common 11.7 kb deletion (exons 4-10). 

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.