Paraganglioma (PGL) Genetic Screening Program at UPCI

Genetic Testing:

Genetic testing is an important component of clinical services when there is concern that paraganglioma(s) in an individual or family may be caused by variants in the genes that have been implicated in hereditary paraganglioma, SDHB, SDHC, SDHD. For more specific information on these genes, please visit our Research Activities section.

Clinical testing by DNA sequence analysis is available for each of these genes through our CLIA-licensed laboratory in the Division of Molecular Diagnostics. There is a charge for clinical testing which may or may not be covered by health insurance plans. Depending on clinical history and other factors, it is often possible to predict which gene is more likely to harbor a disease-causing variant, thus reducing the amount of testing. For relatives of patients who are already known to carry a particular variant, direct testing only for that variant can be performed.

After testing has been explained to the patient and a plan has been formulated with the referring physician, genetic counselor and patient, a 5-10 ml (<1/2 fluid ounce) sample of blood is obtained by venipuncture and DNA isolated from white blood cells. Specific regions of chromosomal DNA containing segments of the gene(s) of interest are chemically-amplified to make analysis easier, and the DNA sequence is obtained and analyzed. Results are reported to the referring physician and/or genetic counselor for disclosure to the patient in 4-10 weeks.

The results of testing may indicate that a patient carries a DNA variant in the SDHB, SDHC, or SDHD gene which has been associated with paraganglioma in other families or in other members of that particular patient’s family. Because paragangliomas are relatively rare tumors on which information is still being collected, results occasionally reveal previously-unreported DNA sequence variants. These variants are reported as such with an indication of how likely they are to be associated with disease (likely, not likely, uncertain). Testing of other relatives, particularly those known to have paraganglioma, can be helpful in clarifying whether a previously unreported variant may be responsible for disease. Finally, results may also disclose the presence of previously described DNA sequence variants which are known from prior studies to NOT be associated with paraganglioma.

At-risk relatives of individuals with an identified disease-causing mutation may benefit from genetic testing whether there is a positive family history or not. Testing enables the clinician to identify individuals with significant risk of developing PGL and to employ radiographic screenings on a selective basis as well as to not employ such measures in those lacking a mutation known to be present in a family. Early detection of paragangliomas and early intervention should decrease the risks of surgery. The substantial genetic component in the development of PGL can often be obscured by imprinting and low-gene penetrance (i.e., some susceptible gene-carrier individuals may not develop tumors until advanced ages).

To obtain further information about clinical genetic testing, please contact:

Abigail Byrnes MS
Genetic Counselor
800-454-8155
412-641-4171
email: abyrnes@mail.magee.edu