Comprehensive Testing from Blood (NF21)
Mendelian Inheritance in Man number: 101000
Click here for Gene Reviews Clinical Summary.
Bilateral Acoustic Neurofibromatosis, Central Neurofibromatosis
Neurofibromatosis type 2 is characterized by bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss and balance dysfunction. Other findings include meningiomas of the brain, schwannomas of other cranial nerves or of the dorsal roots of the spinal cord and juvenile posterior subcapsular cataract. NF2 is an autosomal dominant disorder with a frequency of 1:33-40,000 births in all populations. About 50% of patients are due to a de novo mutation, where neither parent has signs of the disorder. The offspring of an affected individual have a 50% risk of inheriting the altered NF2 gene.
INDICATIONS FOR TESTING
- Confirmatory diagnostic testing
- Testing in an affected patient to prepare for predictive testing and early detection of at-risk relatives for management reasons
- Predictive testing for early detection of at-risk individuals for management reasons
- Testing in an affected patient to prepare for prenatal diagnosis and/or pre implantation diagnosis
We offer a direct test using an RNA/cDNA-based direct sequencing of the entire coding region and MLPA analysis to detect copy number changes. Copy number changes are confirmed by long range RT-PCR, quantitative PCR and/or aCGH.
Using this approach, mutation detection rate in leukocytes is 93% in non-founder NF2 patients. Mutations detected include truncating mutations (nonsense, frameshift, splicing mutations including deep intronic splice mutations), missense mutations, multi-exon deletions or duplications and total gene deletions.
In about 25-30% of founders (simplex cases, patients with unaffected parents), mutations are not detected in blood lymphocytes as a result of somatic mosaicism. Only mutations with mosaicism levels greater than 10% can be detected in lymphocyte DNA (Evans et al, 2007). Identification of the majority of mosaic mutation requires testing of tumor tissue (Evans et al, 2007); more information can be found under NF24, testing from tumor tissue.
In certain circumstances when it is impossible for the MGL to receive a fresh blood sample within 60-72 hours of blood draw, the MGL offers a DNA-based sequence analysis only starting from DNA extracted from an EDTA blood sample. Please note that the comprehensive testing using an RNA/cDNA-based core assay complemented with copy number analysis is more sensitive and specific, and therefore the preferred method. The mutation detection rate in non-founder NF2 patients is 92% using the RNA/cDNA based core assay and copy number analysis approach; whereas it is 90% using the DNA based exon by exon sequencing complemented with copy number analysis [Messiaen L and Evans G, unpublished results].
We require 10 milliliters of whole blood. Blood samples must be collected in EDTA (purple topped) tubes. For pediatric patients or those for whom venipuncture is very difficult, please send a minimum of 3 mL in EDTA.
DNA extracted from an EDTA blood sample (when it is impossible to ship a fresh blood sample.)
If specimen is from clinics within UAB or Kirklin Clinic, please call 934-5562 for pick-up.
Blood specimens must be kept at room temperature and received within 60-72 hours of collection.
1. DO NOT ship on ice.
2. Be sure that the shipping air bill is marked “Priority”, either Domestic or International.
3. 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.
4. Please contact us (Email –firstname.lastname@example.org, Phone – 205-934-5562) prior to sample shipment and provide us with the date of shipment and the tracking number of the package, so that we can better ensure receipt of the samples within the 60-72 hour window.
TURN AROUND TIME
Normal service: 25 working days
RUSH testing: 15 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 NF2 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
- No phenotypic checklist
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.
Baser M, Friedman J, Aeschliman D, Joe H, Wallace A, Ramsden R, Evans DG - Predictors of the risk of mortality in neurofibromatosis 2. Am J Hum Genet 71:715. 2002 (pubmed)
Evans DG, Ramsden RT, Gokhale C, Bowers N, Huson SM, Wallace A Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma? Clin Genet. 71 (4): 354-8, 2007 (pubmed)
Kluwe L, Nygren A, Errami A, Heinrich B, Matthies C, Tatagiba M, Mautner V Screening for large mutations of the NF2 gene. Genes Chromosomes Cancer 42:384, 2005 (pubmed)