Neurofibromatosis 1 von Recklinghausen Syndrome Kristin Neitzke

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Neurofibromatosis 1 von Recklinghausen Syndrome
Kristin Neitzke
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Huang Chunsai
http//www.youtube.com/watch?vxeJBdeNd1x0feature
related
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What is it?

• Inherited disorder affecting nervous system
• Affects 1 in 3,500 worldwide usually children
• 50 of cases inherited, 50 sporadic

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Symptoms of NF1

• Symptoms begin between birth and age 10

http//webhome.idirect.com/nfso/symptoms.jpg
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Most Common Symptoms
Lisch Nodules
Café-au-lait Spots
http//www.science.room.net/geneticdisordersimages
/Neurofibromotosis/cafe20au20Lait20spots20neuo
fib.jpg
http//cc.oulu.fi/anatwww/NF/Neurofibromatosis/li
sch.gif
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The NF1 Gene is Largeand Highly Mutable
http//images.google.com/imgres?imgurlhttp//herk
ules.oulu
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NF1 Encodes Neurofibromin

• Cytoplasmic Protein
• Tumor Suppressor

Gangfeng, 1990
http//en.wikipedia.org/wiki/Neurofibromin_1
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Neurofibromin

• Tumor suppressor
• Cytoplasmic protein
• Has homology with RAS-GTPase activating protein
  (GAP) in mammals

Gangfeng, 1990
http//en.wikipedia.org/wiki/Neurofibromin_1
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How GAP Functions
http//www.wormbook.org/chapters/www_RTKRasMAPKsig
naling/rtkrasfig3.jpg
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How Does Neurofibromin Work?
http//cc.oulu.fi/anatwww/NF/Neurofibromin/Ras.jp
g
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How Does Neurofibromin Work?
http//cc.oulu.fi/anatwww/NF/Neurofibromin/Ras.jp
g
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NF1 in Other Signaling Pathways
http//www.nature.com/ng/journal/v27/n4/fig_tab/ng
0401_354_F1.html
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Knockout Mice Have Heart Defects
Double Outlet Right Ventricle
Normal Heart
Jacks, et al. 1994
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Heterozygous Mutant Miceare 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 tumor formation?

• Loss of neurofibromin in Schwann cell leads to
  tumorigenesis
• LOH is observed in pheochromocytomas and myeloid
  leukemias

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How does loss of NF1 promote tumor formation?

• Plexiform neurofibromas can become malignant
  tumors (5 of cases)
• These often have loss of p53 and mutations in
  INK4 (p16 and Arf)

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Therapies for NF1

• Cochlear Implantation
• Lovastatin
• Drug Therapy (Chemotherapy)
• Traction

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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 102591-7.
• Yuan Z. 2008 cited 2008 Mar 26. Nature
  Genetics. Internet. University of Texas.
  Available from lthttp//images.google.com/imgres?i
  mgurlhttp//www.nature.comgt.
• Jacks T, Shih S, Earlene S. 1994. Tumour
  predisposition in mice heterozygous for a
  targeted mutation in Nf1. Nature 7353-61.
• Dasgupta B, Gutmann D. 2003. Neurofibromatosis 1
  Closing the GAP between mice and men. Current
  Opinion in Genetics and Development 1320-7.
• http//herkules.oulu.fi/isbn9514266463/html/x312.h
  tml
• http//www.understandingnf1.org/exp/int_exp_wci.ht
  ml
• http//www.nfincne.org/uploads/documents/testimony
  .pdf
• http//herkules.oulu.fi/isbn9514271106/html/x239.h
  tml
• http//www.curehunter.com/public/keywordSummaryD00
  9456.do
• http//www.sciencedirect.com/science?
• http//www.understandingnf1.org/exp/int_exp_wci.ht
  ml
• http//www.curehunter.com/public/keywordSummaryD00
  9456.do