Primary Immunodeficiency (PI) refers to a group of over 400 rare genetic disorders that impair the immune system’s ability to defend against infections. Patients with PI experience recurrent infections, autoimmune complications, and an increased risk of malignancies. These disorders are caused by genetic mutations affecting immune function.

Next-Generation Sequencing (NGS) is an advanced genetic testing method that allows for the simultaneous analysis of multiple genes associated with Primary Immunodeficiency disorders. This technology provides a rapid, cost-effective, and comprehensive approach to identifying genetic variants that contribute to immune dysfunction.

NGS testing is recommended for individuals who experience:

• Frequent, persistent, or severe infections
• A family history of Primary Immunodeficiency disorders
• Autoimmune conditions with an unclear genetic basis
• Poor response to standard treatments for infections
• Unexplained low white blood cell counts or immune dysregulation

• Comprehensive Analysis – Screens multiple PI-related genes in a single test
• High Accuracy – Identifies single nucleotide variants (SNVs), insertions/deletions, and copy number variations (CNVs)
• Early Diagnosis – Enables timely medical intervention and treatment planning
• Personalized Treatment – Helps tailor therapies based on the genetic profile
• Family Screening – Assists in identifying at-risk family members for early intervention

1. Sample Collection – A blood or saliva sample is taken at a certified laboratory or healthcare facility.
2. DNA Extraction & Sequencing – DNA is extracted and analyzed using NGS technology to detect genetic mutations.
3. Bioinformatics Analysis – Advanced software interprets genetic variants and their relevance to Primary Immunodeficiency.
4. Clinical Report – A geneticist reviews the results, and a report is provided to the patient’s healthcare provider for further guidance.

Genes Commonly Tested in PI NGS Panels

NGS panels for Primary Immunodeficiency typically analyze genes associated with:

• Antibody Deficiencies (e.g., BTK, IGHM, TNFRSF13B)
• Combined Immunodeficiencies (e.g., IL2RG, ADA, RAG1/RAG2)
• Phagocytic Defects (e.g., CYBB, NCF1, NCF2)
• Complement Deficiencies (e.g., C1QA, C2, C3)
• Autoinflammatory Disorders (e.g., MEFV, NLRP3, TNFAIP3)

Interpreting the Results

• Pathogenic Variant Detected – Indicates a known disease-causing mutation; management strategies will be recommended.
• Likely Pathogenic Variant – Suggests a probable disease association requiring further clinical correlation.
• Variant of Uncertain Significance (VUS) – Requires additional research and family testing for clarification.
• No Pathogenic Variants Detected – Does not completely rule out PI but reduces genetic predisposition likelihood.

• Your healthcare provider will review the results and discuss treatment or preventive strategies.
• Genetic counseling may be recommended to help you understand the implications of your results.
• In some cases, additional tests may be required for further clarification.

Insurance & Cost

NGS testing for PI may be covered by insurance based on medical necessity. Check with your provider for details. Out-of-pocket costs may vary based on the panel size and additional bioinformatics analysis required.

✅ Advanced NGS Technology – State-of-the-art sequencing methods for accurate genetic profiling.
✅ Certified Laboratory – Tests performed in CLIA-certified and CAP-accredited facilities.
✅ Comprehensive Panels – Covers all major PI-associated genes for thorough analysis.
✅ Fast Turnaround Time – Results available within 2-4 weeks.
✅ Expert Genetic Counseling – Professional support to interpret and act on results.