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GNAS Mutation Analysis Test

Last updated Feb. 1, 2017

The GNAS Mutation Analysis Test is a genetic test that detects abnormalities in the GNAS gene. It is used to diagnose hormonal problems.


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

  • Adenylate Cyclase Stimulatory Protein, Alpha Subunit Mutation Analysis Test
  • Guanine Nucleotide Regulatory Protein Mutation Analysis Test
  • Neuroendocrine Secretory Protein 55 Mutation Analysis Test

What is GNAS Mutation Analysis Test? (Background Information)

  • GNAS mutation refers to an alteration in the GNAS gene. It is associated with many metabolic, developmental, skin, and skeletal system disorders
  • The GNAS gene gives instructions for a portion of a protein called G protein (guanine nucleotide-binding protein). The portion for which GNAS gives instructions is the stimulatory alpha subunit - one of the 3 subunits that make up a G protein; the rest are the gamma and beta subunits
  • G proteins are essential to the communication of cells. They serve to amplify signals received by receptors on the cell, allowing cells to make rapid and widespread changes to their production of hormones
  • After they receive a signal by the receptor, G proteins stimulate an enzyme called adenylate cyclase through the action of the stimulatory alpha subunit, whose instructions are provided by the GNAS gene
  • Adenylate cyclase then activates the production of hormones that affect the thyroid, ovaries, pituitary gland, and testes. It also controls bone development and prevents the formation of bone at abnormal locations
  • An alteration in the GNAS gene may result in a G protein whose stimulatory alpha subunit is defective, making it unable to stimulate adenylate cyclase. This may create a diverse array of problems stemming from abnormal hormone production
  • The GNAS Mutation Analysis Test is a genetic test that detects abnormalities in the GNAS gene. It is used to diagnose hormonal problems. It also aids in the treatment of hormonal problems 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 GNAS Mutation Analysis Test?

Following are the clinical indicators for performing the GNAS Mutation Analysis Test: 

  • McCune-Albright syndrome (MAS)
  • Osteitis fibrosa disseminata
  • PFD, POFD
  • Polyostotic fibrous dysplasia
  • Precocious puberty with polyostotic fibrosis and abnormal pigmentation
  • Weight gain and fatty tissue deposits:
    • In the midsection and upper back
    • In the face (moon face)
    • Between the shoulders (buffalo hump)
  • Pink or purple stretch marks (striae) on the skin of the abdomen, thighs, breasts and arms
  • Abnormal bone formation
  • Thinning, fragile skin that bruises easily
  • Slow healing of cuts, insect bites, and infections
  • Acne
  • Thicker or more visible body and facial hair (hirsutism)
  • Irregular or absent menstrual periods
  • Decreased libido, decreased fertility, erectile dysfunction
  • Severe fatigue, muscle weakness
  • Depression, anxiety, and irritability
  • Loss of emotional control
  • Cognitive difficulties
  • New or worsened high blood pressure
  • Headache
  • Bone loss, leading to fractures over time
  • In children, impaired growth

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 GNAS Mutation Analysis Test?

Following is the specimen collection process for GNAS 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

Note:

  • 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 GNAS 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 GNAS Mutation Analysis Test Result?

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

  • McCune-Albright syndrome
  • Cushing syndrome

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:

  • GNAS mutation most notably occurs in a location of the chromosome called 20q13.32 i.e., the long arm (q) of chromosome 20 in position 13.32
  • 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 of 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?

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/cushing-syndrome/

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

http://www.dovemed.com/common-procedures/procedures-laboratory/

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)

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

Mayo Clinic. (2016, March 26). Symptoms and causes - Cushing syndrome. Retrieved from http://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/dxc-20197177

National Organization for Rare Disorders (NORD). (2017). McCune Albright Syndrome. Retrieved from https://rarediseases.org/rare-diseases/mccune-albright-syndrome/

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

Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., ... & Ozenberger, B. A. (2014). Age-related mutations associated with clonal hematopoietic expansion and malignancies. Nature medicine, 20(12), 1472-1478.

Date, K., Ohtsuka, T., Fujimoto, T., Gotoh, Y., Nakashima, Y., Kimura, H., ... & Oda, Y. (2015). GNAS and KRAS mutational analyses of intraductal papillary neoplasms of the pancreas and bile duct developing in the same individual: A case report. Pancreatology, 15(6), 713-716.

Majumder, S., Chari, S. T., & Ahlquist, D. A. (2015). Molecular detection of pancreatic neoplasia: Current status and future promise. World Journal of Gastroenterology: WJG, 21(40), 11387.

Fecteau, R. E., Lutterbaugh, J., Markowitz, S. D., Willis, J., & Guda, K. (2014). GNAS mutations identify a set of right-sided, RAS mutant, villous colon cancers. PloS one, 9(1), e87966.

Takatani, R., Molinaro, A., Grigelioniene, G., Tafaj, O., Watanabe, T., Reyes, M., ... & Jüppner, H. (2015). Analysis of multiple families with single individuals affected by pseudohypoparathyroidism type Ib (PHP1B) reveals only one novel maternally inherited GNAS deletion. Journal of Bone and Mineral Research.

Jour, G., Oultache, A., Sadowska, J., Mitchell, T., Healey, J., Nafa, K., & Hameed, M. (2016). GNAS mutations in fibrous dysplasia: a comparative study of standard sequencing and locked nucleic acid PCR sequencing on decalcified and nondecalcified formalin-fixed paraffin-embedded tissues. Applied Immunohistochemistry & Molecular Morphology, 24(9), 660-667.

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: Feb. 1, 2017
Last updated: Feb. 1, 2017