1. Neurofibromatosis 1 von Recklinghausen Syndrome Kristin Neitzke

2. Huang Chunsai http://www.youtube.com/watch?v=xeJBdeNd1x0 &feature=related

3. What is it? Inherited disorder affecting nervous system Inherited disorder affecting nervous system Affects 1 in 3,500 worldwide usually children Affects 1 in 3,500 worldwide usually children ~50% of cases inherited, 50% sporadic ~50% of cases inherited, 50% sporadic

4. Symptoms of NF1 Symptoms begin between birth and age 10 Symptoms begin between birth and age 10 http://webhome.idirect.com/~nfso/symptoms.jpg

5. Most Common Symptoms Café-au-lait Spots http://www.science.room.net/geneticdisordersimages/Neurofibromotosis/cafe%20 au%20Lait%20spots%20neuofib.jpg Lisch Nodules http://cc.oulu.fi/~anatwww/NF/Neurofibromatosis/lisch.gif

6. The NF1 Gene is Large and Highly Mutable http://images.google.com/imgres?imgurl=http://herkules.oulu

7. NF1 Encodes Neurofibromin Cytoplasmic Protein Cytoplasmic Protein Tumor Suppressor Tumor Suppressor http:// en.wikipedia.org/wiki/Neuro fibromin_1 Gangfeng, 1990

8. Neurofibromin Tumor suppressor Tumor suppressor Cytoplasmic protein Cytoplasmic protein Has homology with RAS-GTPase activating protein (GAP) in mammals Has homology with RAS-GTPase activating protein (GAP) in mammals http:// en.wikipedia.org/wiki/Neuro fibromin_1 Gangfeng, 1990

9. How GAP Functions http://www.wormbook.org/chapters/www_RTKRasMAPKsignali ng/rtkrasfig3.jpg

10. How Does Neurofibromin Work? http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg

11. How Does Neurofibromin Work? http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg

12. NF1 in Other Signaling Pathways http://www.nature.com/ng/journal/v2 7/n4/fig_tab/ng0401_354_F1.html

13. Knockout Mice Have Heart Defects Double Outlet Right VentricleNormal Heart Jacks, et al. 1994

14. Heterozygous Mutant Mice are Predisposed to Tumors  Survival curve of a population of 52 +/+ and 40 +/- animals  Tumors were observed in 8 +/+ and 30+/- animals

15. How does loss of NF1 promote tumor formation? Loss of neurofibromin in Schwann cell leads to tumorigenesis Loss of neurofibromin in Schwann cell leads to tumorigenesis LOH is observed in pheochromocytomas and myeloid leukemias LOH is observed in pheochromocytomas and myeloid leukemias

16. How does loss of NF1 promote tumor formation? Plexiform neurofibromas can become malignant tumors (5% of cases) Plexiform neurofibromas can become malignant tumors (5% of cases) These often have loss of p53 and mutations in INK4 (p16 and Arf) These often have loss of p53 and mutations in INK4 (p16 and Arf)

17. Therapies for NF1 Cochlear Implantation Lovastatin Drug Therapy (Chemotherapy) Traction

18. Sources Upadhyaya M. 1998. "Gross Deletions of the Neurofibromatosis Type 1 (NF1) Gene are Predominantly of Maternal Origin and Commonly Associated with a Learning Disability, Dysmorphic Features and Developmental Delay.". Human Genetics 102:591-7. Upadhyaya M. 1998. "Gross Deletions of the Neurofibromatosis Type 1 (NF1) Gene are Predominantly of Maternal Origin and Commonly Associated with a Learning Disability, Dysmorphic Features and Developmental Delay.". Human Genetics 102:591-7. Yuan Z. 2008 [cited 2008 Mar 26]. Nature Genetics. [Internet]. University of Texas. Available from:. Yuan Z. 2008 [cited 2008 Mar 26]. Nature Genetics. [Internet]. University of Texas. Available from:. Jacks T, Shih S, Earlene S. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nature 7:353-61. Jacks T, Shih S, Earlene S. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nature 7:353-61. Dasgupta B, Gutmann D. 2003. Neurofibromatosis 1: Closing the GAP between mice and men. Current Opinion in Genetics and Development 13:20-7. Dasgupta B, Gutmann D. 2003. Neurofibromatosis 1: Closing the GAP between mice and men. Current Opinion in Genetics and Development 13:20-7. http://herkules.oulu.fi/isbn9514266463/html/x312.html http://www.understandingnf1.org/exp/int_exp_wci.html http://www.nfincne.org/uploads/documents/testimony.pdf http://herkules.oulu.fi/isbn9514271106/html/x239.html http://www.curehunter.com/public/keywordSummaryD009456.do http://www.sciencedirect.com/science? http://www.understandingnf1.org/exp/int_exp_wci.html http://www.curehunter.com/public/keywordSummaryD009456.do