Neurofibromatosis. By Nilesh Jambhekar. What is Neurofibromatosis? The basics:. Autosomal-dominant genetic disorder. Is a type of cancer of the nervous system that can occur in all 3 germ layers and any organ system.
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By Nilesh Jambhekar
-Neurofibromatosis 2(NF2) 
-is on chromosome 17 on the long arm (q) at position 11.2
-has 60 exons and over 8500 base pairs
-encodes for Neurofibromin
A young boy
There are many known mutations of Neurofibromin but the most serious involve the mutations of the above 3 residues (Glutamic acid, Lysine, and especially Arganine).
-Is on Chromosome 22 at location q 11-13.1.
-Encodes a protein called MERLIN (Moesin-Ezrin-Radixin-Like Protein)
- Causes a variety of symptoms related to the ear: deafness, ear ringing, and difficulty keeping balance.
- Less common form of NF1 with an
occurrence of ~1/(30000-40000) births in the U.S.
Fig 6 : Receptor Tyrosine Kinases and RAS. The pathway involves the GRB2, a key target for MERLIN.
Fig : The MERLIN-RAS pathway is filled with chains of Kinases and feedback loops.
Fig 9 : H-RAS
In complex with GCP (an analog of GDP)
5.) Li, Wei, Liru You. “Merlin/NF2 Suppresses Tumorigenesis by Inhibiting the E3 Ubiquitin Ligase CRL4DCAF1 in the Nucleus.”Cell 140.4 (2010): 477-90. 29 March 2010.
6.) Klose, Anja, M. RhezaAhmadian. “Selective disactivation of neurofibromin GAP activity in neurofibromatosis type 1 (NF1).” Oxford University Press7.8 (1998): 1261-1268. 29 March 2010.
7.) Dasgupta, Bislab, Laura Dugan. “The Neurofibromatosis 1 Gene Product Neurofibromin Regulates Pituitary AdenylateCyclase-Activating Polypeptide-Mediated Signaling in Astrocytes.”The Journal of Neuroscience 23.26 (2003): 8949-8954. 29 March 2010.
8.) Guha, A, N. Lau. “Ras-GTP levels are elevated in human NF1 peripheral nerve tumors.”Oncogene 12.3 (1996): 507-13. 30 March 2010.
9.) Fraz A. Ismat, Junwang Xu, Min Min Lu and Jonathan A. Epstein. ”The Neurofibromin GAP-related Domain Rescues Endothelial But Not Neural Crest Development in Nf1–/– mice.”
J. Clin. Invest. 116.9 (2006): 2378-2384. 12 April 2010.
10.) NCBI. Molecular Cell Biology. Baltimore: W. H. Freeman and Company, 2000. Print.
11.) Rob te Biesebeke,‡ Ivo M. Krab,§ and Andrea Parmeggian. “The Arginine Finger Loop of Yeast and Human GAP Is a Determinant for the Specificity toward Ras GTPase.” Biochemistry.40.25 (2001): 7474–7479. 3 April 2010.
12.) David J. Panka1, Wei Wang2, Michael B. Atkins1 and James W. Mier1. “The Raf Inhibitor BAY 43-9006 (Sorafenib) Induces Caspase-Independent Apoptosis in Melanoma Cells.” Cancer Research 66 (2006) 1611-19. 13 April 2010.