What is Neurofibromatosis?
Neurofibromatosis is one of the most common inherited genetic neurological disorders [1]. It is caused by an autosomal dominant mutation on a single gene. Neurofibromatosis is characterized by tumor growth along the nervous system, including the brain, spinal cord, nerves and skin[2]. Neurofibromatosis Type 1 (NF1) is one of three classifications of Neurofibromatosis, and is the most prevalent. NF1 occurs is approximately 1 out of every 3,000 births worldwide[2].
What are the symptoms of
The symptoms of Neurofibromatosis vary wildly on a person to person basis. Even in families the degree of severity is vastly different from parent to child. Typical symptoms of NF1 are café au lait (light brown) skin spots, freckling in the armpits or groin areas, and neurofibromas (small benign growths) on or under the skin [4]. Often children with NF1 have learning disabilities, issues with bone growth and development with possible scoliosis. Most often the tumor growths are benign but some may become malignant and cancerous. Other issues may arise when growth of tumors occur on the spinal cord, in the brain, or nerves. About half of the patients with NF1 also have learning challenges [4].
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Neurofibromatosis Type 1
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What is the treatment for
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Diagnosis is available through blood tests, or a clinical diagnosis from a physician. The diagnostic criteria for NF1 is listed below, an individual must have two or more of the following:
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There is no current prevention or cure for Neurofibromatosis Type 1. In most cases Neurofibromatosis results in mild symptoms and individuals can live normal and productive lives. However some cases need more attention. Tumors can be removed through surgery, although most are benign. If cancer develops from tumors chemotherapy or radiation are recommended as treatment. There is ongoing research and clinical trials for prevention, treatment and/or cures for Neurofibromatosis. [2]
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Foundations and
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What causes Neurofibromatosis Type 1?
A mutation in the NF1 gene, which is located on chromosome 17, is the cause for Neurofibromatosis. This mutation can occur anywhere along the gene and does not seem to show preference to any portions or protein domains. NF1 mutations are autosomal dominant, meaning if a parent has the disease then their children have a 50% chance of getting it. However there can be a difference in severity between parent's and child's appearance of symptoms. There is also a chance of random mutation in a germ cell (egg or sperm) resulting in a diseased person with two healthy parents. Mutations in NF1 are present in all races and both sexes equally [2].
What does the normal NF1 gene do?The normal NF1 gene product is a protein, neurofibromin, that regulates tumor growth. The protein is rather large, approximately 320 kDa. The regular protein is a signal regulator of cell proliferation and differentiation. Neurofibromin is a protein involved in the Ras pathway, it is a negative regulator of the Ras kinase [5]. The protein does this by acting through the interaction of its GTPase-activating protein (GAP)-related domain (GRD) with the product of the Ras protooncogene [6]. Neurofibromin has also been implicated in the activation of the enzyme, adenyl cyclase (AC), that turns adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP), which is used for intracellular signal transduction [5].
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What are the RASopathies?
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References
[1] Neurofibromatosis: Just Ask Foundation
[2] National Human Genome Research Institute: Learning About Neurofibromatosis.
[3] National Institute of Neurological Disorders and Stroke: Neurofibromatosis Information Page
[4] Children's Tumor Foundation
[5] Corral, T., Jimenez, et al. (2003), NF1 modulates the effects of raw oncogenes: Evidence of other NF1 function besides its GAP activity. J. Cell. Physical., 197: 214-224. doi:10.1002/jcp.10349
[6] Caption AJ, French BL, Skuse GR. A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors. American Journal of Human Genetics. 1997;60(2):305-312.
[2] National Human Genome Research Institute: Learning About Neurofibromatosis.
[3] National Institute of Neurological Disorders and Stroke: Neurofibromatosis Information Page
[4] Children's Tumor Foundation
[5] Corral, T., Jimenez, et al. (2003), NF1 modulates the effects of raw oncogenes: Evidence of other NF1 function besides its GAP activity. J. Cell. Physical., 197: 214-224. doi:10.1002/jcp.10349
[6] Caption AJ, French BL, Skuse GR. A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors. American Journal of Human Genetics. 1997;60(2):305-312.
Figures
Figure 1: Neurofibromatosis Type 1 Symptoms. http://www.imagineeringart.com/item/medical-injuries-and-diseases014/
Figure 2: U.S. National Library of Medicine: NF1 Gene
Figure 3: Ratner, Nancy, Miller, Shyra J. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nature Reviews Cancer 15. 2015. http://www.nature.com/nrc/journal/v15/n5/full/nrc3911.html
Video 1: What are the RASopathies? YourekaScience. https://youtu.be/EqLtxzKehC4
Figure 2: U.S. National Library of Medicine: NF1 Gene
Figure 3: Ratner, Nancy, Miller, Shyra J. A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor. Nature Reviews Cancer 15. 2015. http://www.nature.com/nrc/journal/v15/n5/full/nrc3911.html
Video 1: What are the RASopathies? YourekaScience. https://youtu.be/EqLtxzKehC4