SCHWANNOMATOSIS/ATYPICAL TERATOID/RHABDOID TUMOR PREDISPOSITION SYNDROME
Comprehensive Testing from Blood (SB11)
Mendelian Inheritance in Man number: 162091
Click here for Gene Reviews Clinical Summary.
Schwannomatosis is a rare condition characterized by multiple schwannomas and absence of involvement of the vestibular nerve. Schwannomas can arise wherever Schwann cells occur, in the spinal cord and along peripheral and cranial nerves. The tumors manifest most commonly with pain and/or neurological deficit. Some patients with multiple non-vestibular nerve schwannomas and a negative family history are mosaic for NF2. In contrast, a subgroup of patients in whom schwannomas are largely confined to the peripheral nerves, do not have an underlying NF2 mutation, but have schwannomatosis. These individuals may pass the condition on to their children.
Recently, germline mutations in the SMARCB1 gene have been identified in families with schwannomatosis as well as in sporadic schwannomatosis patients (Hulsebos et al, 2007; Sestini et al, 2008; Hadfield et al, 2008). Mutations in SMARCB1 occur in ~33% of familial schwannomatosis patients and in ~7% of sporadic schwannomatosis patients (Hadfield et al, 2008).
Constitutional SMARCB1 mutations are also the cause of inherited predisposition to rhabdoid tumors (Sevenet et al, 1999).
SMARCB1 encodes a member of the chromatin-remodelling SWI/SNF multiprotein complexes.
INDICATIONS FOR DIRECT TESTING
- Individuals with multiple schwannomas without involvement of the vestibular nerve and no NF2 mutation after comprehensive NF2 mutation analysis in the blood
- predictive testing for early detection of at-risk relatives for management reasons
- Individuals with rhabdoid tumors
- Individuals who seek confirmation of a clinical diagnosis
We offer a direct test resulting in the full characterization of the SMARCB1 mutation.
Comprehensive RNA-based testing involves direct sequencing of the RNA and DNA in tandem. From a fresh EDTA blood sample, DNA is extracted and a PHA-stimulated lymphocyte culture is initiated and used to extract mRNA. The extracted DNA and RNA are used as the starting material for direct sequencing of the entire coding region. Mutations screened for include truncating mutations (nonsense, frameshift, splicing mutations) and missense mutations. In addition, copy number alterations (multi-exon deletions or duplications) are analyzed by MLPA.
Alternatively, we offer a direct test from DNA extracted from an EDTA blood sample, although RNA-based testing is the preferred method. Some splice mutations will remain undetected using this approach. Testing includes direct sequencing of all exons and flanking intronic sequence (-20 to +10 minimum) and copy number analysis by MLPA. Please be advised that DNA only testing and test codes will only be used in the event that a fresh blood sample cannot be obtained.
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.
If specimen is from clinics within UAB or Kirklin Clinic, please call 934-5562 for pick-up. If specimens are being sent from some other location, please ship via UPS or Federal Express.
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. Please include the form for customs. This is especially important for samples sent from outside the
TURN AROUND TIME
Test 1: 25 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 SMARCB1 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 if being paid for by an institution
- No informed consent
- No phenotypic checklist
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.
Hadfield KD, Newman WG, Bowers NL, Wallace A, Bolger C, Colley A, McCann E, Trump D, Prescott T, Evans DG Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis J Med Genet 2008 45 (6): 332-9 (pubmed)
Hulsebos TJ, Plomp AS, Wolterman RA, Robanus-Maandag EC, Baas F, Wesseling P Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet. 2007 80 (4): 805-10. (pubmed)
Sestini R, Bacci C, Provenzano A, Genuardi M, Papi L Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas Hum Mutat 2008 29 (2): 227-31. (pubmed)
Sevenet N, Lellouch-Tubiana A, Schofield D, Hoang-Xuan K, Gessler M, Birnbaum D, Jeanpierre C, Jouvet A, Delattre O Spectrum of hSNF5/INI1 somatic mutations in human cancer and genotype-phenotype correlations Hum Mol Genet 1999 8 (13): 2359-68 (pubmed)