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Department of Genetics Heersink School of Medicine

Acceptable specimen types:

  • Blood (2-3ml EDTA; no time limitations associated with receipt)
  • Saliva (OGR-575 DNA Genotek; kits are provided upon request),
  • DNA (extracted from lymphocyte cells, a minimum of 3μg, O.D. value at 260:280nm ≥1.8)
  • Fresh or Frozen Tumor (3-5mm-cubed, >70% pure tumor material)
Turnaround time:

  • 25 working days (Blood/Saliva/DNA)
  • 30 working days (Fresh/Frozen Tumor)
Candidates for this test:

  • Patients with multiple schwannomas w/wo vestibular schwannomas. This testing approach is developed to diagnose mosaic NF2, classic NF2, Schwannomatosis, and mosaic schwannomatosis.
TEST DESCRIPTION

The Meningiomatosis/Multiple meningiomas panel by NGS involves the simultaneous sequencing of 4 genes: NF2, SMARCB1, SMARCE1, and SUFU. The test uses the same approach as detailed above (see: NF1-only by NGS). The average coverage is 2000x with >99.5% of the coding region covered at ≥350x and 99.2% covered at 200x. The minimum coverage for any additional areas is >30x. This allows for detection of very low level mosiacism by sequencing (as low as 8% of the alleles in all regions analyzed by NGS; >99% of the coding region does provide deeper coverage with the ability to identify substitution variants as low as 3% of the alleles). Variant and copy number calls are made using a unique bioinformatics pipeline detecting all types of mutations including single nucleotide substitutions, indels and frameshifts caused by deletion or duplication up to 112bp. Deletion/duplication analysis for NF2 and SMARCB1 is included in this test, as such mutations are a part of the mutation spectrum for these conditions. Deletion/duplication analysis for the other genes on this panel is not offered as current empirical and biological evidence is not sufficient to allow the conclusion that an altered copy number of these genes is a mechanism critical for the phenotype associated with these conditions.

Validation of the full panel included, besides substitutions (missense, nonsense, splice variants), the most challenging mutations such as insertions/deletions/duplications of 1-112bp  and one-to-multiple exon deletions/duplications. The analytical sensitivity of our NGS testing approach was 100% for substitutions as well as insertion/deletions up to 112bp. This panel has not yet been validated to identify deletions/duplications >112bp and <1 exon, but such mutations have not yet been found in the UAB cohort, and therefore are likely very rare. The panel has been validated for the detection of germline (heterozygous) single-exon deletions/duplications as well as multi-exon deletions/duplications, however mosaic single-exon deletion/duplications validation is still pending. 

Relevant family members of a proband with any (novel or previously identified) variant of unknown significance are offered free of charge targeted analysis as long as accurate phenotypic data are provided by a health care professional to enhance the interpretation. There is no limitation to the number of relatives that can be tested free of charge.

For patients presenting with phenotypes that may overlap with both neurofibromatosis type 2 and meningiomatosis, genetic analysis of the associated tumors may be beneficial in determining a diagnosis. While classic and mosaic NF2 presents with biallelic inactivation of the NF2 gene in the tumor material, meningiomatosis can be caused by multiple genetic etilogies. Based on genetic pattern seen in tumors associated with meningiomatosis, tumor based analysis may be able to confirm a diagnosis of meningiomatosis, chromosome 22 involvement, or mosaic NF2 based on the mutations identified in the tumor specimen. 

Tumor based analysis can be performed on fresh or frozen tumor via next-generation sequencing. If the tumor specimen has been formalin-fixed paraffin embedded (FFPE) tumor, please review our Sanger sequencing 




SPECIMEN SHIPPING AND HANDLING:

  • Please find specimen requirement specifications above.
  • All submitted specimens must be sent at room temperature. DO NOT ship on ice.
  • 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 company’s diagnostic envelope).
  • To request a sample collection kit, please click here or email medgenomics@uabmc.edu to complete the specimen request form.
  • Please contact the MGL (via email at medgenomics@uabmc.edu, or via phone at 205-934-5562) prior to sample shipment and provide us with the date of shipment and tracking number of the package so that we can better ensure receipt of the samples.
REQUIRED FORMS

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 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
For more information, test requisition forms, or sample collection and mailing kits, please call: 205-934-5562.

Other related test options: