Paraganglioma Genes Sequencing

Familial paraganglioma is a rare syndrome characterized by slow-growing tumors derived from paraganglia tissue in the head and neck, thorax, abdomen, and pelvis. Research has shown that mutations in three genes (SDHB, SDHC, and SDHD) encoding subunits of succinate dehydrogenase (SDH), or mitochondrial complex II, are responsible for most cases of familial paraganglioma.

The SDH Mutation Database tool, based on the Leiden Open (source) Variation Database system at http://chromium.liacs.nl/lovd_sdh/, provides an overview of all known SDH mutations and the associated tumor types.

Mutations in SDHD, chromosome locus 11q23, 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.

Mutations in SDHB, chromosome locus 1p35–36, are primarily associated with paragangliomas in the abdomen, pelvis, and thorax, although head and neck tumors. Patients with SDHB mutations are at increased risk for malignant paraganglioma and may be at increased risk for renal cell carcinoma and papillary thyroid cancer.

Mutations in SDHC, chromosome locus 1q21, have been reported in families with head and neck parasympathetic paragangliomas. Inheritance of SDHC mutations does not demonstrate the parent of origin effect observed in families with SDHD mutations.

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.

Methodology: Sequencing of entire coding region

Purpose: Confirmation of Clinical Diagnosis/Carrier Testing

Test Requisition: Sequencing Requisition

SDHB CPT Code: 81405Cost: $763.00

SDHD CPT Code: 81404 Cost: $333.00

SDHC CPT Code: 81405 Cost: $763.00

SDHAF2 CPT Code: 81479 Cost: $548.00

If sequencing all four Paraganglioma genes total cost $2278.00

Turn-around-time: 3-4 weeks for each test