Preferred initial test when hereditary paraganglioma-pheochromocytoma is suspected.
- Patient Preparation
- Lavender (EDTA), 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: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
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 SDHB, SDHC, and SDHD, predispose to paraganglioma and pheochromocytoma with risk of malignant transformation.
Incidence: About 1 in 300,000 per year.
Inheritance: Autosomal dominant; parent of origin effect for SDHD.
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: 26-30 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHB, SDHC, and SDHD genes; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large SDHB, SDHC, and 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 SDHB, SDHC, and SDHD are not evaluated.
|Component Test Code*||Component Chart Name||LOINC|
|2007168||HPGL-PCC (SDHB,C,D) Seq, DelDup Specimen||31208-2|
|2007169||HPGL-PCC (SDHB,C,D) Seq, DelDup Interp||41103-3|
- Hereditary Paraganglioma-Pheochromocytoma molecular assay
- Paraganglioma (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- PCC (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- PGL (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- Pheochromocytoma (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- SDHB, SDHC, and SDHD Sequencing and Deletion/Duplication
- SDHB, SDHC, SDHD Genes
- Stromal Tumor (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplication
- Succinate Dehydrogenase genetic assay
- Succinate Dehydrogenase, subsets B, C, and D (SDHB, SDHC, and SDHD) Sequencing and Deletion/Duplicat