Diagnostic Test Directory

Molecular Genetics Laboratory

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Hereditary Paraganglioma (SDH5 Sequence Analysis)

  • Synonyms: SDHAF2

    Collect

    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also accepted.

    Volume Required

    5 ml whole blood or 1 ug extracted DNA

    Minimum Required

    3 ml whole blood

    Transport

    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.

    Stability

    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm

Reported

3 - 4 weeks

CPT

81479

Disease Information

Clinical Features:

Paraganglioma syndrome includes inherited head and neck paragangliomas (HNPs) and adrenal or extra-adrenal pheochromocytomas. Hereditary paragangliomas belong to a group of dominantly inherited disorders characterized by the development of highly vascularized, nonchromaffin tumors arising in parasympathetic ganglia, usually in the head and neck. Up to 50% of paragangliomas are familial, and multiple loci are known to be involved.

Molecular Genetics:

The genes responsible for familial paraganglioma / pheochromocytoma (PGL/PCC) syndromes encode three of the four subunits of the succinate-dehydrogenase (SDH) mitochondrial enzyme complex: SDHB, SDHC and SDHD (testing for these genes is available in the MGL Laboratory). In 2009, a missense mutation (p.Gly78Arg) in a fourth nuclear gene, SDH5 (also known as SDHAF2) was identified in affected members of a large Dutch family. SDH5 consists of four exons that encode for a protein that appears to be required for SDHA flavination, stability of the SDH complex, and therefore the function of the SDH enzyme. Initial data suggests that mutations in SDH5 exhibit parent-of-origin effects similar to those of mutations in the SDHD gene (disease is generally caused only if the mutation is inherited from the father).

Test Methods:

We offer DNA sequence analysis of the SDH5 gene. PCR amplification and sequencing is performed on all coding exons including splice junctions. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.

Related Tests:

Known mutation analysis is available to family members for previously identified mutations. We offer the following tests related to Paraganglioma and/ or Pheochromocytoma: Hereditary Paraganglioma Panel (SDHB/C/D Sequencing and Deletion Analysis) Multiple Endocrine Neoplasia type 2 - MEN2A and MEN2B analysis (exons 16 -19) Von-Hippel-Lindau Disease – VHL Gene Sequencing and Deletion Analysis

Results:

Test results with interpretation will be mailed and/or faxed to the referring physician or send out lab following completion of the test. Additional reports will be provided as requested.

Utility:

Molecular diagnosis of affected individuals allows pre-symptomatic screening of at risk family members and leads to early detection and timely intervention in the disease process.

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215-590-5221