neurofibromatosis 1 von recklinghausen syndrome kristin neitzke
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Neurofibromatosis 1 von Recklinghausen Syndrome Kristin Neitzke. Huang Chunsai. http://www.youtube.com/watch?v=xeJBdeNd1x0&feature=related. What is it?. Inherited disorder affecting nervous system Affects 1 in 3,500 worldwide usually children ~50% of cases inherited, 50% sporadic. - PowerPoint PPT PresentationTRANSCRIPT
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Neurofibromatosis 1 Neurofibromatosis 1
von von RecklinghausenRecklinghausen SyndromeSyndrome
Kristin Neitzke Kristin Neitzke
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Huang Chunsaihttp://www.youtube.com/watch?v=xeJBdeNd1x0&feature=related
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What is it?What is it?
Inherited disorder affecting nervous systemInherited disorder affecting nervous system
Affects 1 in 3,500 worldwide usually childrenAffects 1 in 3,500 worldwide usually children
~50% of cases inherited, 50% sporadic~50% of cases inherited, 50% sporadic
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Symptoms of NF1Symptoms of NF1
• Symptoms begin Symptoms begin between birth and between birth and age 10age 10
http://webhome.idirect.com/~nfso/symptoms.jpg
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Most Common SymptomsMost Common Symptoms
Café-au-lait Spots
http://www.science.room.net/geneticdisordersimages/Neurofibromotosis/cafe%20au%20Lait%20spots%20neuofib.jpg
Lisch Nodules
http://cc.oulu.fi/~anatwww/NF/Neurofibromatosis/lisch.gif
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The NF1 Gene is LargeThe NF1 Gene is Largeand Highly Mutableand Highly Mutable
http://images.google.com/imgres?imgurl=http://herkules.oulu
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NF1 Encodes NeurofibrominNF1 Encodes Neurofibromin
• Cytoplasmic ProteinCytoplasmic Protein• Tumor SuppressorTumor Suppressor
http://en.wikipedia.org/wiki/Neurofibromin_1
Gangfeng, 1990
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NeurofibrominNeurofibromin
• Tumor suppressorTumor suppressor• Cytoplasmic proteinCytoplasmic protein• Has homology with Has homology with
RAS-GTPase RAS-GTPase activating protein activating protein (GAP) in mammals(GAP) in mammals
http://en.wikipedia.org/wiki/Neurofibromin_1
Gangfeng, 1990
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How GAP FunctionsHow GAP Functions
http://www.wormbook.org/chapters/www_RTKRasMAPKsignaling/rtkrasfig3.jpg
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How Does Neurofibromin Work?How Does Neurofibromin Work?
http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg
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How Does Neurofibromin Work?How Does Neurofibromin Work?
http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg
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NF1 in Other Signaling PathwaysNF1 in Other Signaling Pathways
http://www.nature.com/ng/journal/v27/n4/fig_tab/ng0401_354_F1.html
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Knockout Mice Have Heart DefectsKnockout Mice Have Heart Defects
Double Outlet Right VentricleNormal Heart
Jacks, et al. 1994
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Heterozygous Mutant MiceHeterozygous Mutant Miceare Predisposed to Tumorsare Predisposed to Tumors
Survival curve of a population of 52 +/+ and 40 +/- animals
Tumors were observed in 8 +/+ and 30+/- animals
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How does loss of NF1 promote How does loss of NF1 promote tumor formation?tumor formation?
• Loss of neurofibromin in Schwann cell Loss of neurofibromin in Schwann cell leads to tumorigenesisleads to tumorigenesis
• LOH is observed in pheochromocytomas LOH is observed in pheochromocytomas and myeloid leukemiasand myeloid leukemias
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How does loss of NF1 promote How does loss of NF1 promote tumor formation?tumor formation?
• Plexiform neurofibromas can become Plexiform neurofibromas can become malignant tumors (5% of cases)malignant tumors (5% of cases)
• These often have loss of p53 and These often have loss of p53 and mutations in INK4 (p16 and Arf)mutations in INK4 (p16 and Arf)
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Therapies for NF1Therapies for NF1
• Cochlear Implantation• Lovastatin• Drug Therapy (Chemotherapy)• Traction
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SourcesSources• Upadhyaya M. 1998. "Gross Deletions of the Neurofibromatosis Type 1 (NF1) Gene Upadhyaya M. 1998. "Gross Deletions of the Neurofibromatosis Type 1 (NF1) Gene
are Predominantly of Maternal Origin and Commonly Associated with a Learning are Predominantly of Maternal Origin and Commonly Associated with a Learning Disability, Dysmorphic Features and Developmental Delay.". Human Genetics Disability, Dysmorphic Features and Developmental Delay.". Human Genetics 102:591-7.102:591-7.
• Yuan Z. 2008 [cited 2008 Mar 26]. Nature Genetics. [Internet]. University of Texas. Yuan Z. 2008 [cited 2008 Mar 26]. Nature Genetics. [Internet]. University of Texas. Available from: Available from: <http://images.google.com/imgres?imgurl=http://www.nature.com>. <http://images.google.com/imgres?imgurl=http://www.nature.com>.
• Jacks T, Shih S, Earlene S. 1994. Tumour predisposition in mice heterozygous for a Jacks T, Shih S, Earlene S. 1994. Tumour predisposition in mice heterozygous for a targeted mutation in Nf1. Nature 7:353-61.targeted mutation in Nf1. Nature 7:353-61.
• Dasgupta B, Gutmann D. 2003. Neurofibromatosis 1: Closing the GAP between mice Dasgupta B, Gutmann D. 2003. Neurofibromatosis 1: Closing the GAP between mice and men. Current Opinion in Genetics and Development 13:20-7. 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