Known Mutation Testing (KT2)
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 (Hadfiedl 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
- Predictive testing for early detection of at-risk relatives for management reasons
We offer a targeted detection of a previously characterized SMARCB1 mutation within the family. Depending on the mutation identified previously in the family, targeted testing can involve FISH analysis, direct sequencing of a specific region or copy number analysis by MLPA. From a fresh EDTA blood sample, DNA is extracted directly and the target region is amplified and analyzed for presence or absence of the specific mutation.
Test 2 is provided free of charge to all relevant relatives of a proband in whom a novel missense alteration was found that needs further clarification to come to a final conclusion. As the final conclusion on the pathogenicity of a missense alteration relies on accurate phenotypic data, the testing in relevant relatives is provided free of charge only if a phenotypic checklist is filled out by a healthcare professional that made the clinical assessment of the relatives. The correct interpretation of the results also relies on the correct disclosure of the biological relationships.
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 934-5562 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 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: we offer free of charge targeted testing to all relevant relatives of a proband in whom a novel missense variant was identified. Testing of these relatives may allow us to make a final conclusion on the pathogenicity of the novel missense variant and allow us to provide better counseling now and in the future. Free of charge targeted testing will only be provided if the necessary phenotypic information on the proband and relatives filled out by a healthcare professional accompanies the samples. If no phenotypic information is provided, we will charge the institution for the test.
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)