Neurofibromatosis is an autosomal dominant disorder characterised by café-au-lait spots and fibromatous tumours of the skin. Neurofibromatosis type I is caused by defects in the NF1 gene on chromosome 17q11.2. This gene encodes neurofibromin 1, a cytoplasmic protein predominantly expressed in neurons, Schwann cells and leukocytes. Neurofibromatosis type II is caused by defects in the NF2 gene on chromosome 22q12.2.
Deletions of part of the NF1 gene as well as deletions and duplications of the complete NF1 gene have been described. Relatively common (5-10% of NF1 cases) is a deletion of a 1500 kb chromosomal region that includes the NF1 gene. This interstitial 17q11.2 microdeletion arises from unequal crossover between 2 highly homologous 60-kb duplicons. Phenotype of the 17q11.2 microdeletion is usually much more severe than most other NF1 cases and may include severe developmental delay.
The NF1 gene (58 exons) spans ~283 kb of genomic DNA and is located on chromosome 17q11.2. This P122-D1 NF1 area MLPA probemix contains 20 probes for 16 genes located at close distance to NF1 as well as probes for 5 distinct NF1 exons. In addition, 8 references probes are included in this probemix, detecting several different autosomal chromosomal locations. Note that the P081 and P082 probemixes contain probes for each individual NF1 exon.
This SALSA® MLPA® probemix is designed to detect deletions/duplications of one or more sequences in the aforementioned region in a DNA sample. Heterozygous deletions of recognition sequences should give a 35-50% reduced relative peak height of the amplification product of that probe. Note that a mutation or polymorphism in the sequence detected by a probe can also cause a reduction in relative peak height, even when not located exactly on the ligation site! In addition, some probe signals are more sensitive to sample purity and small changes in experimental conditions. Therefore, deletions and duplications detected by MLPA should always be confirmed by other methods. Not all deletions and duplications detected by MLPA will be pathogenic; users should always verify the latest scientific literature when interpreting their findings. We have no information on what percentage of defects in these genes is caused by deletions/duplications of complete exons. Finally, note that most defects in this gene are expected to be small (point) mutations which will not be detected by this SALSA® MLPA® test.