Diagnostic Test Directory

Molecular Genetics Laboratory

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Von Hippel-Lindau (VHL Sequence and Deletion Analysis)

  • Synonyms: Von Hippel's Disease
  • LIS Mnemonic: MBVHLSCRN


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

    Volume Required

    5 ml whole blood or 2 ug extracted DNA

    Minimum Required

    3 ml whole blood


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


    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


4-6 weeks


81403, 81404

Disease Information

Clinical Features:

von Hippel-Lindau disease (VHL) is a cancer predisposition syndrome characterized by the development of hemangioblastomas of the brain, spinal cord, and retina; renal cysts and clear cell renal cell carcinoma; pheochromocytoma; and endolymphatic sac tumors. Renal cell carcinoma occurs in about 40% of patients and is the leading cause of mortality. The diagnosis of VHL syndrome is suspected in individuals with two characteristic lesions (including hemangioblastomas, renal cysts and renal cell carcinoma, pheochromocytoma, and endolymphatic sac tumors) or a single lesion and a positive family history. Early detection of VHL syndrome may allow for intervention and improved outcome as well as facilitate pre-symptomatic screening for family members since 80% of VHL mutations are inherited (20% are de novo mutations).

Molecular Genetics:

VHL is the only gene known to be associated with VHL syndrome. The VHL tumor suppressor gene is located on chromosome 3p26-p25. The inheritance pattern is autosomal dominant. Molecular genetic testing of the VHL gene detects mutations in nearly 100% of affected individuals. Approximately 72% of VHL mutations are point mutations detected by sequence analysis. Approximately 28% of VHL mutations are partial or complete gene deletions detectable by multiplex ligation-dependent probe amplification assay.

Test Methods:

We offer DNA sequence analysis and deletion/duplication testing of the entire coding region. These tests can be ordered together as a panel or separately. 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. Large deletions and duplications in the VHL gene will be detected using multiplex ligation-dependent probe amplification assay (MLPA).

Detection Rate:

Full screening of the VHL gene consists of sequence analysis of all three coding exons (72%) and deletion/duplication analysis by MLPA to detect complete or partial gene deletions (responsible for 28% of all cases). The analytical sensitivity for MLPA and sequencing is close to 100%.

Related Tests:

Known mutation analysis of the VHL gene is available to family members for mutations previously identified by sequence analysis or deletion/duplication analysis. Prenatal Testing is available to individuals who are confirmed carriers of mutations in the VHL gene. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen. We offer the following tests related to Renal Cell Carcinoma: Hereditary leiomyomatosis and renal carcinoma- FH Gene Sequencing and Deletion Analysis Birt-Hogg-Dube – FLCN Gene Mutation Screen Hereditary papillary renal carcinoma – MET proto-oncogene We offer the following tests related to Pheochromocytoma: Hereditary Paraganglioma – SDHB sequence and deletion analysis Hereditary Paraganglioma – SDHC sequence and deletion analysis Hereditary Paraganglioma – SDHD sequence and deletion analysis Multiple Endocrine Neoplasia type 2 - MEN2A and MEN2B analysis


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


The clinical utility of these assays is to confirm a clinical diagnosis of VHL, facilitate pre-symptomatic testing of at risk relatives, rule out VHL in individuals with limited expression of disease, confirm the need for clinical surveillance in patients positive for a mutation, and to facilitate prenatal diagnosis.

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