Known Mutation Testing (KT2)
Mendelian Inheritance in Man number: 193300
Click here for Gene Reviews Clinical Summary.
VHL syndrome is an autosomal dominant disorder with a high penetrance (almost complete by 60 years of age) characterized by hemangioblastomas in central nervous system (CNS), retina and other visceral organs. This disorder is also associated with an increased risk of other tumors including clear cell carcinomas of the kidney, pheochromocytoma, renal cysts, pancreatic cystadenoma and pancreatic neuroendocrine tumors. VHL affects ~ 1:35,000 individuals. World-wide prevalence of VHL is approximately 1: 36,000 live births. All ethnic groups and both sexes are affected equally.
Genetics of VHL
The official name for the VHL gene is von Hippel-Lindau tumor suppressor, which resides on chromosome 3p25.3. VHL gene contains 3 exons and encodes a ~ 4.5 kb mRNA. Loss of function mutations in VHL are the only known cause of VHL, and germline VHL mutations can be detected in up to 100% of VHL families. Germline mutations are scattered throughout the coding region of the gene. Missense mutations (leading to an amino acid substitution in the VHL protein product) are found in 40 % of the families with an identified VHL germline mutation. Microdeletions (1-18 bp.), insertions (1-8 bp.), splice site and nonsense mutations, predicted to lead to a truncated protein, are found in approximately 30 % of the families. Large deletions account for one-third of the VHL germline mutations, of which approximately 30 % (or some 10 % of all VHL germline mutations) are deletions encompassing the entire gene. The de novo mutation rate is estimated at 20% and mosaicism may occur in a small percentage of VHL patients.
INDICATIONS FOR DIRECT TESTING
- Identification of pre-symptomatic carriers of a VHL-associated mutation among family members of patients.
- Exclusion of the diagnosis and thus eliminating unnecessary clinical testing among family member who are shown not to carry their family’s VHL mutation.
We offer a targeted detection of a previously characterized VHL mutation within the family. Depending on the mutation identified previously in the family, targeted testing can involve direct sequencing of a specific region or copy number analysis by MLPA.
We require 1 milliliter of whole blood. Blood samples must be collected in EDTA (purple topped) tubes.
If specimen is from clinics within UAB or Kirklin Clinic, please call 934-7107 for pick-up. If specimens are being sent from some other location, please ship via UPS or Federal Express.
1. Be sure that the shipping air bill is marked “Priority”, either Domestic or International.
2. Specimens must be packaged to prevent breakage and absorbent material must be included in the package to absorb liquids in the event that breakage occurs. Also, the package must be shipped in double watertight containers (e.g. a specimen pouch + the shipping companies Diagnostic Envelope). You can use our collection kits, which we will send to physicians directly upon request.
TURN AROUND TIME
10 working days
CPT CODES AND PRICES
Please find the most up to date prices and CPT codes for our testing services under the "Prices" tab of this website.
Note: Detailed and accurate completion of this document is necessary for reporting purposes. The Medical Genomics Laboratory issues its clinical reports based on the demographic data provided by the referring institution on the lab requisition form. It is the responsibility of the referring institution to provide accurate information. If an amended report is necessary due to inaccurate or illegible documentation, additional reports will be drafted with charge.
Requests for Molecular Genetic testing for VHL will not be accepted for the following reasons:
- No label (patients full name and date of collection) on the specimens
- No referring physician’s or genetic counselor’s names and addresses
- No billing information
- No informed consent
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.
Maher ER, Webster AR, Richards FM, Green JS, Crossey PA, Payne SJ, Moore AT (1996). Phenotypic expression in von Hippel-Lindau disease: correlations with germline VHL gene mutations. J Med Genet 33:328–32 (pubmed)
Richards FM, Payne SJ, Zbar B, Affara NA, Ferguson-Smith MA, Maher ER (1995) Molecular analysis of de novo germline mutations in the von Hippel-Lindau disease gene. Hum Mol Genet 4:2139–43 (pubmed)
Stolle C, Glenn G, Zbar B, Humphrey JS, Choyke P, Walther M, Pack S, Hurley K, Audrey C, Klausner R, Linehan WM (1998) Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum Mutat 12:417–23. (pubmed)
Yoshida M, Ashida S, Kondo K, Kobayashi K, Kanno H, Shinohara N, Shitara N, Kishida T, Kawakami S, Baba M, Yamamota I, Hosaka M, Shuin T, Yao M (2000) Germ-line mutation analysis in patients with von Hippel-Lindau disease in Japan: an extended study of 77 families. Jpn J Cancer Res 91:204–12 (pubmed)