Neurofibromatosis NGS panel
||NGS panel with CNV analysis
||2-4 ml of blood with anticoagulant EDTA
1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Indications for genetic testing:
1. Confirmation of clinical diagnosis
2. Differential diagnosis of neurofibromatosis types and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
4. Genetic counseling
Neurofibromatosis (NF) is a group of neurocutaneous syndromes characterized by generally non-cancerous tumors in the nervous system and skin. The tumors involve the supporting cells of the nervous system rather than the neurons. There are three types of NF:
1) NF1 is characterized by skin changes (cafe-au-lait spots, freckling in armpit and groin area), bone abnormalities, optic gliomas, and tumors on the nerve tissue or under the skin. Signs and symptoms are usually present at birth.
2) NF2 is characterized by acoustic neuromas, hearing loss, tinnitus, loss of balance, brain and/or spinal tumors, cataracts at a young age, secondary to bilateral vestibular schwannomas, and may have café-au-lait macules. NF2 often starts in the teen years.
3) Schwannomatosis (SWN) is characterized by multiple schwannomas (benign tumors of the nervous system) and, less frequently, meningiomas. Signs and symptoms of the condition vary based on the size, location and number of schwannomas but may include chronic pain, numbness, tingling, and/or weakness in the fingers and toes. SWN often develops during adulthood between ages 25 and 30.
The diagnosis of NF types is typically based on symptoms, examination, medical imaging, and biopsy.
The test covers known genetic causes of inherited forms of NF and a range of disorders with NF symptoms. Currently, many of the causative genes have not been identified yet.
All three types of NF are inherited in an autosomal dominant pattern. About 50% of NF1 and NF2 patients have a de novo mutation, and the other half have an inherited mutation. NF1 and NF2 have a nearly 100% penetrance with variable expressivity. Unlike most other autosomal dominant conditions, two copies of the NF1 and NF2 gene must be altered to trigger tumor formation in NF1 and NF2, respectively. A somatic mutation in the second copy of the NF1 gene or the NF2 gene occurs during a person’s lifetime in cells of the nervous system.
Inherited forms of the SWN account for 15% of all cases with highly variable expressivity and reduced penetrance (50%).
NF1 consisting of about 96% of all NF cases with a worldwide prevalence of 1:3000. NF2 consisting of about 3% of all NF with a worldwide prevalence between 1:25000 and 1:40000. SWN is the rarest type out of these three conditions with a worldwide prevalence 1:69000.
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