Neurofibromatosis Type 2 via the NF2 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
4041 NF2 81406 81406,81405 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4041NF281406 81405, 81406 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Neurofibromatosis Type 2 (NF2, OMIM 101000) is a tumor predisposition syndrome with bilateral vestibular schwannoma (BVS) as the hallmark. Patients with NF2 may also develop schwannoma at other locations and other tumors such as meningioma, glioma, neurofibroma, astrocytoma and skin tumors. Posterior subcapsular lens opacities are common in NF2. Other common symptoms include hearing loss, imbalance, tinnitus, facial weakness and headache (Parry et al. Am J Med Genet 52:450-461, 1994; Kanter et al. Neurology 30:851-859, 1980). Two clinical subtypes are recognized. A severe subtype, also called the Wishart subtype, is characterized by an early onset, severe features, rapid progression, and predisposition to meningioma and spinal tumors, in addition to the BVS. A mild subtype, also known as Gardner subtype, has a later onset, a comparatively benign course, and a low incidence of meningioma and spinal tumors (Bruder et al. Hum Mol Genet 10:271-282, 2001). NF2 is a panethnic disease with an incidence of approximately 1 in 56,000 live births (Evans et al. Am J Med Genet A 152A:327-332, 2010).

Genetics

Mutations in the NF2 gene cause NF2 (Trofatter et al. Cell 72:791-800, 1993; Rouleau et al. Nature 363:515-521, 1993). In about half of cases, NF2 is inherited as an autosomal dominant trait, with high penetrance. In the remaining half, NF2 is caused by de novo mutations (Evans et al. J Med Genet 29:841-846, 1992). About 25 % of patients with sporadic NF2 are mosaic (Evans et al. Am J Hum Genet 63:727-736, 1998; Kluwe et al. J Med Genet 40:109-114, 2003). To date, about 400 NF2 germline mutations were reported. Nonsense and frameshift mutations represent the majority of mutations and have been associated with the severe NF2 subtype. However, somatic mosaicism of such mutations may result in milder phenotype. Missense mutations, small in-frame insertions or deletions, and gross deletions have been associated with the milder phenotype (Selvanathan. Clin Genet 77(2):163-170, 2010). Splicing mutations have been associated with phenotypic variability, including intrafamilial variability (Kluwe et al. Am J Med Genet 77:228-33, 1998). NF2 encodes the Merlin protein, a tumor-suppressor.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test detects mutations in ~ 73% of patients with an established family history of NF2 and ~ 60% of sporadic cases (Evans et al. J Med Genet 44:424-428, 2007). Somatic mosaicism is likely to account for the lower mutation detection rate in patients with sporadic NF2 (Evans et al. Am J Hum Genet 63:727-736, 1998).

Testing Strategy

This test provides full coverage of all coding exons of the NF2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients presenting with a clinical diagnosis of NF2 according to the NIH criteria and presymptomatic testing of family members in NF2 families with known mutations.

Gene

Official Gene Symbol OMIM ID
NF2 607379
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Neurofibromatosis, Type 2 AD 101000

Related Tests

Name
Cancer Panel
Familial Meningioma via the SMARCE1 Gene

Citations

  • Bruder, C. E., et.al. (2001). "High resolution deletion analysis of constitutional DNA from neurofibromatosis type 2 (NF2) patients using microarray-CGH." Hum Mol Genet 10(3): 271-82. PubMed ID: 11159946
  • Evans, D. G., et.al. (1992). "A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity." J Med Genet 29(12): 841-6. PubMed ID: 1479598
  • Evans, D. G., et.al. (1998). "Somatic mosaicism: a common cause of classic disease in tumor-prone syndromes? Lessons from type 2 neurofibromatosis." Am J Hum Genet 63(3): 727-36. PubMed ID: 9718334
  • Evans, D. G., et.al. (2007). "Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification." J Med Genet 44(7): 424-8. PubMed ID: 17307835
  • Kanter, W. R., et.al. (1980). "Central neurofibromatosis with bilateral acoustic neuroma: genetic, clinical and biochemical distinctions from peripheral neurofibromatosis." Neurology 30(8): 851-9. PubMed ID: 6774282
  • Kluwe L, Mautner V, Heinrich B, Dezube R, Jacoby LB, Friedrich RE, MacCollin M. 2003. Molecular study of frequency of mosaicism in neurofibromatosis 2 patients with bilateral vestibular schwannomas. Journal of medical genetics 40: 109–114. PubMed ID: 12566519
  • Parry, D. M., et.al. (1994). "Neurofibromatosis 2 (NF2): clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity." Am J Med Genet 52(4): 450-61. PubMed ID: 7747758
  • Rouleau, G. A., et.al. (1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2." Nature 363(6429): 515-21. PubMed ID: 8379998
  • Selvanathan et al. Further genotype--phenotype correlations in neurofibromatosis 2. Clin Genet. 77(2):163-70, 2010. PubMed ID: 19968670
  • Trofatter, J. A., et.al. (1993). "A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor." Cell 72(5): 791-800. PubMed ID: 8453669

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

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Requisition Form

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  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

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