Hereditary Paraganglioma-Pheochromocytoma (SDHB) Sequencing and Deletion/Duplication

Background Information for Hereditary Paraganglioma-Pheochromocytoma (SDHB) Sequencing and Deletion/Duplication:
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, predispose to paraganglioma and pheochromocytoma with risk of malignant transformation.
Incidence: About 1 in 300,000 per year.
Inheritance: Autosomal dominant.
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: 7-11 percent.
Methodology: Bidirectional sequencing of all coding regions and intron-exon boundaries of the SDHB gene; Multiplex Ligation-dependent Probe Amplification (MLPA) to detect large SDHB 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 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.