Hereditary Paraganglioma (PGL) is characterized by slow-growing tumors derived from paraganglia tissue in the head and neck, thorax, abdomen, and pelvis. Pheochromocytomas (PCC) are a type of paraganglioma that is confined to the adrenal gland, a small hormone producing organ located on top of each kidney.
Research has shown that mutations in several genes (SDHB, SDHC, SDHD, SDHA, SDHAF2, and MAX) encoding subunits of succinate dehydrogenase (SDH), or mitochondrial complex II, are responsible for most cases.
We provide testing for the genes listed below that are believed to be associated with paragangliomas and pheochromocytomas. SDHA, SDHB, SDHC, SDHD, SDHAF2, MAX, TMEM127, & VHL.
||Mutations have been identified in multigenerational families with primarily head and neck parasympathetic paragangliomas. SDHD mutations predispose to the development of multifocal paragangliomas. In patients with SDHD mutations, penetrance depends on whether the individual inherited the mutation from the mother or the father. The disease is not manifested when the mutation is inherited from the mother, but is highly penetrant when inherited from the father. Chromosome locus 11q23. Mutations account for 50% of patients with PGL.
||Mutations in SDHAF2, chromosome locus 11q12.2, has been identified in people with hereditary paraganglioma-pheochromocytoma. People with this condition have paragangliomas, pheochromocytomas, or both. Analysis recommended if no mutations observed in SDHD, SDHC, or SDHB genes.
||Found in families with head and neck parasympathetic paragangliomas. Inheritance of mutations does not demonstrate the parent of origin effect observed in families with SDHD mutations. Benign tumors observed with mutations of SDHC. Chromosome locus 1q21.
||Associated with paragangliomas in abdomen, pelvis, thorax, head and neck tumors. Mutations put patients at risk for malignant paragangliomas, renal cell carcinoma, and papillary thyroid cancer. Mutations account for 38-40% of patients with PGL. Chromosome locus 1p35–36.
||Mutations associated with Leigh syndrome. Only 3 mutations have been identified on chromosome 3q29.
The MAX gene encodes a protein that regulates cell growth and division. Mutations in this gene were identified in 8.5 percent of patients with either bilateral PCC or early age of onset of PCC. Mutations account for 1% of patients with PGL. Chromosome locus 14q23. Analysis recommended if no mutations observed in SDHD, SDHC, or SDHB genes.
Purpose: Confirm a genetic basis for cancer/Identify at-risk family members
Methodology: Next-Generation Sequencing
Test Requisition: Sequencing Requisition
Specimen Requirements: 2-5 mL Blood-Lavender Top Tube
Panel CPT Codes: 81437 Panel Price: $3500.00
Turn-around-time: 6 weeks
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8. Mu, W, et al. "Sanger confirmation is required to achieve optimal sensitivity and specificity in next-generation sequencing panel testing". J Mol Diagn. 2016. 18(6):923-932.