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SALSA® MLPA® Probemix P044 NF2 detects copy number variations in the NF2 gene.
Contents: 43 MLPA probes, including 21 probes for NF2, 5 probes for genes upstream of NF2 , and 4 probes for genes downstream of NF2.
Tissue: genomic DNA isolated from human peripheral whole blood. Research use: genomic DNA from FFPE or fresh tumour tissue.
Application: NF2-related schwannomatosis.
CE-marked for in vitro diagnostic (IVD) use.
The SALSA MLPA Probemix P044 NF2 is an in vitro diagnostic (IVD) or research use only (RUO) semi-quantitative manual assay for the detection of deletions or duplications in the NF2 gene in genomic DNA isolated from human peripheral whole blood specimens. P044 NF2 is intended to confirm a potential cause for and clinical diagnosis of NF2-related schwannomatosis and for molecular genetic testing of at-risk family members. NF2-related schwannomatosis has a high incidence of mosaicism (~15% of patients are mosaic) and mosaic mutations may not be detectable in blood.
For the full intended purpose, see the product description.
NF2-related schwannomatosis (formerly known as Neurofibromatosis type 2) is an autosomal dominant cancer susceptibility/predisposition syndrome that is characterized by the development of bilateral vestibular schwannomas (BVSs) in almost all patients. This disease is caused by inactivating mutations of the neurofibromatosis type 2 (NF2) tumour-suppressor gene. BVSs result in hearing loss, tinnitus and balance dysfunction. The age of onset is between 18 and 24 years. Patients also suffer from schwannomas of other cranial and peripheral nerves, meningiomas, ependymomas, and rarely, astrocytomas. Although most of these tumours are not malignant, their anatomic location and multiplicity lead to high morbidity and mortality at a low age: the average age of death is 36 years. NF2-related schwannomatosis occurs in approximately 1 in 25,000-40,000 live births and the estimated prevalence in the general population is 1 in 50,000 without any known ethnic or racial bias. For known pathogenic mutations the penetrance is close to 100% (Asthagiri et al. 2009).
Mutational analysis of the NF2 gene in typical NF2-related schwannomatosis patients has demonstrated causative mutations in ~70%. The NF2 gene behaves as a typical tumour-suppressor gene, with first hits detectable in both constitutional and tumour specimens and second hits detectable only in tumours. Approximately 50% of NF2 mutation-positive patients inherit a germline mutation from an affected parent and the remaining half are sporadic cases due to de novo mutations. Large alterations affecting the NF2 gene account for 15-20% of all known NF2 mutations (Abo-Dalo et al. 2010; Halliday et al. 2017; Kluwe et al. 2005; Smith et al. 2016). Combined with the 70% NF2 mutation detection rate in patients, this means that in 10-15% of NF2-related schwannomatosis patients large deletions or duplications are detected. A high level of mosaicism is observed in NF2-related schwannomatosis, which can complicate mutation detection. More than 30% of the de novo cases are mosaic for NF2 mutations, which may result in subclinical symptoms and/or difficulties with mutation detection, resulting in a false negative diagnosis (Evans et al. 2007).
Mutations in NF2 are also frequently found in sporadic schwannomas and meningiomas (Lassaletta et al. 2013; Mohyuddin et al. 2002; Pathmanaban et al. 2017). Both NF2-related schwannomatosis syndromic tumours and such sporadic tumours have often lost a large part of chromosome 22 resulting in loss of heterozygosity (LOH) of NF2. These large chromosomal deletions frequently include loss of SMARCB1 and LZTR1, which are also recognized as tumour suppressor genes associated with schwannomatosis.
More information on NF2-related schwannomatosis can be found at https://www.ncbi.nlm.nih.gov/books/NBK1201/ and https://omim.org/entry/101000/.
SALSA MLPA Probemix P044 NF2 is CE-marked for in vitro diagnostic (IVD) use.
This assay is for research use only (RUO) in all other territories.
A general SALSA MLPA Reagent Kit is required for MLPA experiments (to be ordered separately).
Inclusion of a positive sample is usually not required, but can be useful for the analysis of your experiments. MRC Holland has very limited access to positive samples and cannot supply such samples. We recommend using positive samples from your own collection. Alternatively, you can use positive samples from an online biorepository, such as the Coriell Institute.
See this support article for commercially available positive samples that have been tested with this product.