Use when SDHD-related hereditary paraganglioma-pheochromocytoma is suspected.
- Patient Preparation
- Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
- Specimen Preparation
- Transport 3 mL whole blood. (Min: 2 mL)
- Storage/Transport Temperature
- Unacceptable Conditions
- Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Characteristics: Hereditary paraganglioma-pheochromocytoma (PGL/PCC) syndromes are characterized by paragangliomas (neuroendocrine tumors of the autonomic nervous system) and pheochromocytomas (paragangliomas of the adrenal medulla). Pathogenic germline mutations in a number of genes, including SDHD, predispose to paraganglioma and pheochromocytoma.
Incidence: About 1 in 300,000 per year.
Inheritance: Autosomal dominant; disease manifestations generally occur when mutations in SDHD are inherited from the father (but not from the mother) due to a parent of origin effect.
Cause: Pathogenic succinate dehydrogenase, subunits B, C, and D (SDHB, SDHC, and SDHD) gene mutations. Mutations in other genes, including TMEM127, EGLN1, MAX, SDHA, and SDHAF2, may also be causative.
Clinical Sensitivity: 15 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHD gene; multiplex ligation-dependent probe amplification (MLPA) to detect large SDHD deletions/duplications.
Analytical Sensitivity and Specificity: Sequencing: 99 percent. MLPA: 90 and 99 percent, respectively.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. The breakpoints of large deletions/duplications will not be determined. Mutations in genes other than SDHD are not evaluated. This assay is not designed to detect somatic variants associated with malignancy. Interpretation of this test result may be impacted if the patient has had an allogeneic stem cell transplantation.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|2007123||HPGL-PCC (SDHD) Seq, DelDup Specimen||31208-2|
|2007124||HPGL-PCC (SDHD) Seq, DelDup Interp||41061-3|
- Succinate Dehydrogenase genetic assay
- Hereditary PGL/PCC Type 1 molecular assay
- Paraganglioma (SDHD) Sequencing and Deletion/Duplication
- PCC (SDHD) Sequencing and Deletion/Duplication
- PGL (SDHD) Sequencing and Deletion/Duplication
- Pheochromocytoma (SDHD) Sequencing and Deletion/Duplication
- SDHD Gene
- SDHD Sequencing and Deletion/Duplication
- Stromal Tumor (SDHD) Sequencing and Deletion/Duplication
- Succinate Dehydrogenase, subset C (SDHD) Sequencing and Deletion/Duplication