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
Neurofibromatosis 1 Neurofibromatosis 1
von von RecklinghausenRecklinghausen SyndromeSyndrome
Kristin Neitzke Kristin Neitzke
Huang Chunsaihttp://www.youtube.com/watch?v=xeJBdeNd1x0&feature=related
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
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
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
The NF1 Gene is LargeThe NF1 Gene is Largeand Highly Mutableand Highly Mutable
http://images.google.com/imgres?imgurl=http://herkules.oulu
NF1 Encodes NeurofibrominNF1 Encodes Neurofibromin
• Cytoplasmic ProteinCytoplasmic Protein• Tumor SuppressorTumor Suppressor
http://en.wikipedia.org/wiki/Neurofibromin_1
Gangfeng, 1990
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
How GAP FunctionsHow GAP Functions
http://www.wormbook.org/chapters/www_RTKRasMAPKsignaling/rtkrasfig3.jpg
How Does Neurofibromin Work?How Does Neurofibromin Work?
http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg
How Does Neurofibromin Work?How Does Neurofibromin Work?
http://cc.oulu.fi/~anatwww/NF/Neurofibromin/Ras.jpg
NF1 in Other Signaling PathwaysNF1 in Other Signaling Pathways
http://www.nature.com/ng/journal/v27/n4/fig_tab/ng0401_354_F1.html
Knockout Mice Have Heart DefectsKnockout Mice Have Heart Defects
Double Outlet Right VentricleNormal Heart
Jacks, et al. 1994
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
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
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)
Therapies for NF1Therapies for NF1
• Cochlear Implantation• Lovastatin• Drug Therapy (Chemotherapy)• Traction
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