Diagnostic Test Directory

Molecular Genetics Laboratory

CHOP in the News

Clinical Lab Products quotes Avni Santani, PhD, Scientific Director, Molecular Genetics Laboratory, in a story about next-gen sequencing. Read the story »

Laboratory Update

Testing for the Noonan spectrum of disorders is now available at the Molecular Genetics Laboratory. Learn more about Noonan spectrum testing »

Hereditary Paraganglioma (SDHC-PGL3 Sequencing)

  • Synonyms: Hereditary Paraganglioma-Pheochromocytoma Syndrome
  • LIS Mnemonic: MBSDHCSEQ

    Collect

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

    Volume Required

    5 ml whole blood or 2 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

4-6 weeks

CPT

81405

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. 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.

Molecular Genetics:

Succinate-dehydrogenase is involved in oxidation of succinate to fumarate in the Krebs cycle and in providing electrons to the mitochondrial electron transport chain. SDHC and SDHD proteins anchor complex II in the inner mitochondrial membrane while SDHB encodes one of the two subunits of the catalytic core, the iron-sulphur protein. SDHB (1p25) is composed of eight exons and is approximately 40 kb in length. Nonsense, missense, and splice-site mutations, intragenic deletions and insertions, and whole-gene SDHB deletions have been reported in individuals affected with hereditary paraganglioma syndromes. SDHC (1q21) has six exons and is more than 35 kb in length. Nonsense, missense, splice-site, regulatory, and exon deletions have been reported in individuals affected with hereditary PGL syndromes. SDHD (11q23) consists of four exons that encodes a 1313-bp transcript. Nonsense, missense, splice-site, intragenic insertions and deletions, and a whole-gene deletion have been reported in SDHD in individuals affected with hereditary paraganglioma syndromes.

Test Methods:

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.

Detection Rate:

Approximately 74% of familial cases of head and neck paraganglioma are believed to be caused by germline mutations in one of these three genes (50% in SDHD; 20% in SDHB; 4% in SDHC). Additionally, 13% of families with inherited and extra adrenal sympathetic PGL and PCC have mutations in the SDHD gene, and 24% have mutations in the SDHB gene.

Related Tests:

Sequence analysis of the SDHB and SDHD genes is available. Large deletions and duplications in the SDHB/SDHC/SDHD genes will be detected using multiplex ligation-dependent probe amplification assay (MLPA). Known mutation analysis is available to family members for previously identified mutations. Prenatal Testing is available for individuals who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen. We offer the following tests related to Pheochromocytoma: 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.

Search Lab Test Directory

Search by disease or test name

View a full list of all lab tests

Contact Us

Ask for more information about our laboratory services.

215-590-5221