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PubMed This is a summary of 19 peer-reviewed journal articles Updated
Clinical Immunology

Medical Testing and Understanding Your Reports

At a Glance

Partial STAT1 deficiency is evaluated by combining the STAT1 genetic variant, immune-function tests, clinical history, and the exact mycobacterium identified. Drug susceptibility results can help guide antibiotics, but specialists must interpret all findings together.

Navigating the diagnostic journey for partial STAT1 deficiency involves translating complex lab reports into a clear picture of your health. Because this condition is rare and shares features with other immune disorders, your doctors use a combination of genetic “blueprints” and functional “stress tests” to confirm the diagnosis [1][2].

The Genetic Blueprint (Genetics Reports)

Your genetic report is the foundation of your diagnosis. It looks at the STAT1 gene to see if the instructions for building this protein are correct.

  • Variant Notation: Look for codes like c.1892T>C or p.Val631Ala. These tell you exactly where the “typo” is in your DNA and how it changed the protein [3][4].
  • Classification: A critical part of the report is the classification. A reported STAT1 change may be benign, likely pathogenic, pathogenic, or a Variant of Uncertain Significance (VUS). A VUS means the lab doesn’t yet have enough evidence to prove it causes the disease. Do not make vaccine or treatment decisions based on a VUS alone [1].
  • Zygosity: Heterozygous means you have one mutated copy (typical for the Autosomal Dominant form), while Homozygous or Compound Heterozygous means both copies are affected (typical for the Autosomal Recessive form). Heterozygosity or homozygosity alone does not prove that it causes partial deficiency without functional correlation [1][5][6].
  • Testing Method: Most patients start with an Inborn Error of Immunity (IEI) panel or Whole-Exome Sequencing (WES) (which covers coding regions). If these are inconclusive, your doctor might order Whole-Genome Sequencing (WGS) to find hidden mutations in the “non-coding” parts of the gene, or RNA sequencing to evaluate splicing if the relevant transcript is expressed [1][5][7].

The Cellular Stress Test (Functional Assays)

Knowing you have a mutation is only half the story; your doctors interpret functional assays alongside your genetic and clinical findings. These tests are often performed in specialized research labs [2][8].

  • STAT1 Phosphorylation (pSTAT1): This measures the “spark” mentioned on the Biology page. In partial deficiency, results can vary, and a “normal” result in one assay does not definitively exclude disease [9][4].
  • Nuclear Translocation: This test checks if the STAT1 protein can actually move into the cell’s control center (the nucleus) once it’s activated [10][4].
  • GAS/ISRE Activity: These reports measure if STAT1 can successfully “turn on” the defense genes. These results are interpreted against healthy controls to understand the mutation’s behavior [1][2].

Identifying the Invader (Microbiology Reports)

Because you are susceptible to specific bacteria, “identifying the species” is more than just a formality—it supports your treatment plan [11][12].

  • Species-Level Identification: Your report should specify exactly which mycobacterium is present. For example, distinguishing between M. tuberculosis and M. bovis BCG is vital, as the BCG strain is naturally resistant to certain common TB drugs like pyrazinamide [11][13].
  • Advanced Detection: Since mycobacteria grow very slowly in a dish, doctors may use PCR (DNA matching) or Metagenomic Next-Generation Sequencing (mNGS) to identify the bacteria directly from a tissue sample or blood [14][15].
  • Susceptibility Testing: This part of the report lists which antibiotics work against your specific strain in the lab. This supports the selection of your treatment, though in vitro susceptibility does not guarantee clinical success (site penetration and drug toxicity also matter) [16][17].

Checklist for a Complete Report Review

When reviewing your records, ensure you have the following key pieces of information to share with your care team:

  1. Genetic Variant Classification: The exact mutation and whether it is pathogenic, likely pathogenic, or a VUS [4].
  2. Inheritance Pattern: Whether the variant was inherited or appeared for the first time in you (de novo) [3][18].
  3. Clinical Correlation: How your functional proof and clinical symptoms align with the genetic findings [1][2].
  4. Organism Identity: The exact name of the bacteria or virus causing an infection [16][11].
  5. Drug Susceptibility: A list of medications that the lab found to be most effective to support your treatment selection [16][19].

Common questions in this guide

What does a pathogenic STAT1 variant mean on my genetic report?
A pathogenic or likely pathogenic STAT1 variant is a DNA change that the laboratory believes can disrupt STAT1 function and contribute to partial STAT1 deficiency. Doctors still compare the result with your infection history and immune-function testing, because a genetic result alone does not determine every diagnosis or treatment decision.
How should I interpret a STAT1 variant of uncertain significance?
A variant of uncertain significance means there is not enough evidence to know whether the DNA change affects health. It should not be used by itself to make vaccine or treatment decisions, and your specialist may reassess it if new evidence becomes available.
Can a normal STAT1 phosphorylation test rule out partial STAT1 deficiency?
No. Results can vary between tests, and a normal result in one assay does not definitively exclude partial STAT1 deficiency. Specialists interpret phosphorylation together with other immune-function tests, genetic findings, and your clinical history.
Why does the exact mycobacterium on my report matter?
Identifying the species helps doctors choose treatment. M. tuberculosis and M. bovis BCG are different, and BCG is naturally resistant to pyrazinamide, so the distinction can affect antibiotic selection.
What does drug susceptibility testing tell me?
Drug susceptibility testing shows which antibiotics stop your strain in the laboratory and helps guide treatment selection. A laboratory result cannot guarantee success because drug levels at the infection site, side effects, and other clinical factors also matter.
What is the difference between whole-exome and whole-genome sequencing for STAT1?
Whole-exome sequencing focuses on coding parts of genes, while whole-genome sequencing can also examine non-coding regions. If these tests do not explain the result, RNA sequencing may help show whether a STAT1 change affects how the gene's message is processed when the relevant RNA is available.
Could my relatives need testing for the same STAT1 variant?
If a pathogenic or likely pathogenic STAT1 variant is found, a genetics team may discuss testing parents or siblings because some forms can follow dominant or recessive inheritance patterns. Family testing is individualized and should be planned with a qualified genetics professional.

Get notified when new evidence is published on Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References

References (19)
  1. 1

    Novel STAT1 Variants in Japanese Patients with Isolated Mendelian Susceptibility to Mycobacterial Diseases.

    Ono R, Tsumura M, Shima S, et al.

    Journal of clinical immunology 2023; (43(2)):466-478 doi:10.1007/s10875-022-01396-1.

    PMID: 36336768
  2. 2

    Genetic and Functional Identifying of Novel STAT1 Loss-of-Function Mutations in Patients with Diverse Clinical Phenotypes.

    Chen X, Chen J, Chen R, et al.

    Journal of clinical immunology 2022; (42(8)):1778-1794 doi:10.1007/s10875-022-01339-w.

    PMID: 35976469
  3. 3

    A novel STAT1 loss-of-function mutation associated with Mendelian susceptibility to mycobacterial disease.

    Ye F, Zhang W, Dong J, et al.

    Frontiers in cellular and infection microbiology 2022; (12()):1002140 doi:10.3389/fcimb.2022.1002140.

    PMID: 36339330
  4. 4

    Severe Impairment of IFN-α and IFN-γ Responses in Cells of a Patient with a Rare STAT1 Tail Segment Domain Mutation.

    Xiao J, Qiu J

    Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2025; (45(12)):385-393 doi:10.1177/10799907251389756.

    PMID: 41115717
  5. 5

    Autosomal recessive complete STAT1 deficiency caused by compound heterozygous intronic mutations.

    Sakata S, Tsumura M, Matsubayashi T, et al.

    International immunology 2020; (32(10)):663-671 doi:10.1093/intimm/dxaa043.

    PMID: 32603428
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    Genetic, Immunological, and Clinical Features of 32 Patients with Autosomal Recessive STAT1 Deficiency.

    Le Voyer T, Sakata S, Tsumura M, et al.

    Journal of immunology (Baltimore, Md. : 1950) 2021; (207(1)):133-152 doi:10.4049/jimmunol.2001451.

    PMID: 34183371
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    A rare mutation causing autosomal dominant STAT1 deficiency in a South African multiplex kindred with disseminated BCG infection.

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    BMC pediatrics 2023; (23(1)):378 doi:10.1186/s12887-023-04206-8.

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    Alanine-scanning mutagenesis of human signal transducer and activator of transcription 1 to estimate loss- or gain-of-function variants.

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    The Extended Clinical Phenotype of 26 Patients with Chronic Mucocutaneous Candidiasis due to Gain-of-Function Mutations in STAT1.

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    PMID: 26604104
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    A Positive Feedback Amplifier Circuit That Regulates Interferon (IFN)-Stimulated Gene Expression and Controls Type I and Type II IFN Responses.

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    PMID: 29892288
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    Pediatric Mycobacterium bovis Infection: Clinical Spectrum, BCG-Related Disease, Primary Immunodeficiency, and a Comprehensive Review of the Literature.

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    Vaccines 2026; (14(10)) doi:10.3390/vaccines14100867.

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    What We Have Here Is a Failure to Communicate: Interleukin-12 / Interferon-gamma Axis Defects and Mendelian Susceptibility to Mycobacterial Disease.

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    The journal of allergy and clinical immunology. In practice 2026; (14(7)):1529-1539 doi:10.1016/j.jaip.2026.02.026.

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  13. 13

    Severe BCG-osis Misdiagnosed as Multidrug-Resistant Tuberculosis in an IL-12Rβ1-Deficient Peruvian Girl.

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    Paradigm for diagnosing mycobacterial disease: direct detection and differentiation of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria in clinical specimens using multiplex real-time PCR.

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    A Novel Compound Heterozygous Mutation in the IL12RB1 Gene Causes Susceptibility To Mycobacterium Tilburgii Infection.

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    DISSEMINATED BACILLUS-CALMETTE-GUÉRIN INFECTIONS AND PRIMARY IMMUNODEFICIENCY DISORDERS IN SINGAPORE: A SINGLE CENTER 15-YEAR RETROSPECTIVE REVIEW.

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  18. 18

    Case report: A novel de novo germline loss-of-function mutation in the STAT1 transactivation domain in two Chinese siblings, with the elder sibling presenting with multifocal Bacillus Calmette-Guerin osteomyelitis.

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    Persistent Ascites Revealing Mendelian Susceptibility to Mycobacterial Disease Due to IL-12Rβ1 Deficiency: A Case Report and Review of the Literature.

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This page is for informational purposes only and does not constitute medical advice. Your immunology, genetics, and infectious disease specialists should interpret your reports and make testing or treatment decisions with you.

Guide contents Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency
Research & Literature
03 The Biology of Your Diagnosis and Similar Conditions 05 The Standard of Care and Treatment Approaches