Please Remove Adblock
Adverts are the main source of Revenue for DoveMed. Please remove adblock to help us create the best medical content found on the Internet.

PLCG2 Mutation Analysis Test

Last updated May 31, 2017

Approved by: Maulik P. Purohit MD MPH

The PLCG2 Mutation Analysis Test is a genetic test that helps detect abnormalities in the PLCG2 gene. It is used to diagnose autoimmune disorders.

What are other Names for this Test? (Equivalent Terms)

  • APLAID Mutation Analysis Test
  • `FCAS3 Mutation Analysis Test
  • PLC-Gamma-2 Mutation Analysis Test

What is PLCG2 Mutation Analysis Test? (Background Information)

  • PLCG2 mutation refers to an alteration in the PLCG2 gene. It is associated with autoimmune disease. The PLCG2 gene gives instructions for the PLCG2 protein (phospholipase C gamma 2 protein). PLCG2 is important for communication between cells
  • The PLCG2 protein is an enzyme that resides in the membranes of immune cells. The protein is situated such that one end faces the outside of the cell, and the other end faces the inside
  • Its unique position within the membrane allows PLCG2 to serve as a communication system between a cell of the immune system and other cells in the body
  • When receptors on a cell surface, such as growth factor receptors and immune system receptors, receive their signals, they communicate with PLCG2. PLCG2 then relays their message to the inside of the cell
  • PLCG2 relays messages through chemical means. As an enzyme, PLCG2 causes a chemical reaction to occur that transforms a chemical called PIP2 into two chemicals - IP3 and DAG
  • IP3 and DAG are chemical signals that act inside the cell to affect the conversion of genetic information to proteins, allowing an immune system cell to respond to external signals
  • An alteration in PLCG2 may result in a PLCG2 protein that is defective. Because it is central to the communication of immune cells, a defective PLCG2 protein may lead to disorders in which immune cells falsely recognize cells of the body as being foreign and attack them (autoimmune disease)
  • The PLCG2 Mutation Analysis Test is a genetic test that helps detect abnormalities in the PLCG2 gene. It is used to diagnose autoimmune disorders. It also aids in the treatment of autoimmune disorders by guiding selection of therapeutic drugs, including disqualifying certain drugs from use

The molecular testing, in general, can be performed using a variety of methods. Some of these methods include:

  • In situ hybridization techniques, such as fluorescence in situ hybridization (FISH)
  • Immunohistochemistry (IHC)
  • Next-generation sequencing (NGS)
  • Polymerase chain reaction (PCR)
  • Comparative genomic hybridization (CGH)
  • Karyotyping including spectral karyotyping
  • mRNA analysis
  • Tissue microarrays (TMAs)
  • Southern blot test
  • Northern blot test
  • Western blot test
  • Eastern blot test

The methodology used for the test may vary from one laboratory to another.

Note: Molecular testing has limitations due to the molecular method and genetic mutational abnormalities being tested. This can affect the results on a case-by-case basis. Consultation with your healthcare provider will help in determining the right test and right molecular method, based on individual circumstances.

What are the Clinical Indications for performing the PLCG2 Mutation Analysis Test?

Following are the clinical indications for performing the PLCG2 Mutation Analysis Test: 

  • Fever
  • Rash
  • Joint swelling
  • Bone swelling; bone pain
  • Skeletal deformities

In general, the molecular genetic testing is undertaken in the following situations: 

  • To assist (and in some cases, confirm) the initial diagnosis
  • If there is a family history of the medical disorder/condition
  • To distinguish other conditions that have similar features (signs and symptoms)
  • To help in determining treatment options
  • To confirm recurrence of the tumor: Tumor recurrence can either be at the original tumor site, or at a distant location (away from the initial site)

How is the Specimen Collected for PLCG2 Mutation Analysis Test?

Following is the specimen collection process for PLCG2 Mutation Analysis Test:

The specimen sample requirements may vary from lab to lab. Hence, it is important to contact the testing lab for exact specimen requirements, before initiating the testing process.

  • Sample on which the test is performed may include:
    • Peripheral blood in individuals showing signs and symptoms suspected of TTT
    • In case of expectant mothers, prenatal testing through amniotic fluid and chorionic villi sampling
    • Fresh tumor tissue during biopsy: In some cases, the testing can be performed on tumor tissue also
    • Formalin-fixed paraffin-embedded solid tumor tissue (FFPE tumor tissue), often referred to as paraffin block of the tumor
    • Unstained tissue slides
  • Process of obtaining the sample: As outlined by the laboratory testing facility
  • Preparation required: As outlined by the laboratory testing facility


  • In some cases, a different source of specimen (such as peripheral blood, bone marrow biopsy specimen, or other body fluids) may be acceptable to the laboratory performing the test
  • Occasionally, additional samples may be required to either repeat the test or to perform follow-up testing
  • Depending on the location of testing, it may take up to 2 weeks’ turnaround time, to obtain the test results
  • Many hospitals preserve the paraffin blocks for at least 7 years. In general, older paraffin blocks (over 5 years) may affect the detection of specific mutations, due to degradation of the tumor specimen over time

Cost of PLCG2 Mutation Analysis Test:

  • The cost of the test procedure depends on a variety of factors, such as the type of your health insurance, annual deductibles, co-pay requirements, out-of-network and in-network of your healthcare providers and healthcare facilities
  • In many cases, an estimate may be provided before the test is conducted. The final amount may depend upon the findings during the test procedure and post-operative care that is necessary (if any)

What is the Significance of the PLCG2 Mutation Analysis Test Result?

A mutation in the PLCG2 gene indicates a positive result for the PLCG2 Mutation Analysis Test. This may point to a diagnosis of any of the following:

  • Autoinflammation
  • Antibody deficiency
  • PLCG2-associated immune dysregulation
  • Familial cold autoinflammatory syndrome 3

The laboratory test results are NOT to be interpreted as results of a "stand-alone" test. The test results have to be interpreted after correlating with suitable clinical findings and additional supplemental tests/information. Your healthcare providers will explain the meaning of your tests results, based on the overall clinical scenario.

Additional and Relevant Useful Information:

  • PLCG2 mutation most notably occurs in a location of the chromosome called 16q23.3 i.e., the long arm (q) of chromosome 16 in position 23.3
  • Many laboratories may not have the capability to perform this test. Only highly-specialized labs with advanced facilities and testing procedures may perform this test

Certain medications that you may be currently taking may influence the outcome of the test. Hence, it is important to inform your healthcare provider, the complete list of medications (including any herbal supplements) you are currently taking. This will help the healthcare provider interpret your test results more accurately and avoid unnecessary chances of a misdiagnosis.

What are some Useful Resources for Additional Information?

Please visit our Laboratory Procedures Center for more physician-approved health information:


References and Information Sources used for the Article:

https://ghr.nlm.nih.gov/primer/testing/genetictesting (accessed on 05/10/2017)

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5806a1.htm (accessed on 05/10/2017)

http://www.nature.com/gim/journal/v10/n5/full/gim200852a.html (accessed on 05/10/2017)

http://pediatrics.aappublications.org/content/106/6/1494 (accessed on 05/10/2017)

National Institutes of Health. (n.d.). Autoinflammatory Diseases. Retrieved from https://www.niams.nih.gov/health_info/autoinflammatory/

PLCG2 gene - Genetics Home Reference. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/PLCG2#location

Helpful Peer-Reviewed Medical Articles:

Carrano, A. V., et al. Measurement and purification of human chromosomes by flow cytometry and sorting. Proceedings of the National Academy of Sciences 76, 1382–1384 (1979)

Drets, M. E., & Shaw, M. W. Specific banding patterns of human chromosomes. Proceedings of the National Academy of Sciences 68, 2073–2077 (1971)

Druker, B. J. Perspectives on the development of a molecularly targeted agent. Cancer Cell 1, 31–36 (2002)

Parra, I., & Windle, B. High resolution visual mapping of stretched DNA by fluorescent hybridization. Nature Genetics 5, 17–21 (1993) doi:10.1038/ng0993-17

Pinkel, D., et al. High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nature Genetics 20, 207–211 (1998) doi:10.1038/2524

Speicher, M. R., et al. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12, 368–375 (1996) doi:10.1038/ng0496-368

Ombrello, M. J., Remmers, E. F., Sun, G., Freeman, A. F., Datta, S., Torabi-Parizi, P., ... & Romberg, N. (2012). Cold urticaria, immunodeficiency, and autoimmunity related to PLCG2 deletions. New England Journal of Medicine, 366(4), 330-338.

Aderibigbe, O. M., Priel, D. L., Lee, C. C. R., Ombrello, M. J., Prajapati, V. H., Liang, M. G., ... & Milner, J. D. (2015). Distinct cutaneous manifestations and cold-induced leukocyte activation associated with PLCG2 mutations. JAMA dermatology, 151(6), 627-634.

Gbadegesin, R. A., Adeyemo, A., Webb, N. J., Greenbaum, L. A., Abeyagunawardena, A., Thalgahagoda, S., ... & Chand, D. (2014). HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. Journal of the American Society of Nephrology, ASN-2014030247.

Chae, J. J., Park, Y. H., Park, C., Hwang, I. Y., Hoffmann, P., Kehrl, J. H., ... & Kastner, D. L. (2015). Brief Report: Connecting Two Pathways Through Ca2+ Signaling: NLRP3 Inflammasome Activation Induced by a Hypermorphic PLCG2 Mutation. Arthritis & Rheumatology, 67(2), 563-567.

Gossmann, J., Stolte, M., Lohoff, M., Yu, P., Moll, R., Finkernagel, F., ... & Huynh, M. Q. (2016). A gain-of-function mutation in the Plcg2 gene protects mice from helicobacter felis-induced gastric MALT lymphoma. PloS one, 11(3), e0150411.

Zhou, Q., Lee, G. S., Brady, J., Datta, S., Katan, M., Sheikh, A., ... & Kuhns, D. B. (2012). A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. The American Journal of Human Genetics, 91(4), 713-720.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: May 31, 2017
Last updated: May 31, 2017