Neurofibromatosis 1
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Transcript of Neurofibromatosis 1
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Neurofibromatosis 1Neurofibromatosis 1
Valerie KhodushValerie Khodush
March 27, 2007March 27, 2007
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NF-1 Overview NF-1 Overview
Incidence – 1:3500Incidence – 1:3500 Von Von
Reckinghausen Reckinghausen DiseaseDisease
Tumor pre-Tumor pre-disposing diseasedisposing disease
Protein: Protein: neurofibromin neurofibromin
(220-250kDa)(220-250kDa) Tumor suppressorTumor suppressor
http://www.embl.de/groupOrProgrammeImage/285.jpg
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Remember RasRemember Ras
Gilbert Fig. 6.14
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NF1 is a Ras-GapNF1 is a Ras-Gap
http://www.charite.de/ch/medgen/eumedis/embryology04/neurocutan-disorders/Slide4.png
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Mouse KnockoutMouse Knockout
Embryonic lethal at Embryonic lethal at E12.5 to E13.5E12.5 to E13.5
Cardiovascular Cardiovascular problemsproblems
Organ development Organ development
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Mouse KnockoutMouse Knockout
Heterozygous mice Heterozygous mice develop different develop different cancerscancers
Learning and spatial Learning and spatial memorymemory
Double mutants Double mutants (NF1+/- & p53+/-)(NF1+/- & p53+/-)
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17 Similar to Rb Similar to Rb
functionfunction
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17 Similar to Rb functionSimilar to Rb function Dominant versus Dominant versus
recessive recessive
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17 Similar to Rb functionSimilar to Rb function Dominant versus Dominant versus
recessive recessive Familial/de novo Familial/de novo
inheritance or inheritance or spontaneous mutations spontaneous mutations
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17 Similar to Rb functionSimilar to Rb function Dominant versus Dominant versus
recessive recessive Familial/de novo Familial/de novo
inheritance or inheritance or spontaneous mutations spontaneous mutations
Schwann cells/ LOHSchwann cells/ LOH
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromin Neurofibromin
Chromosome 17Chromosome 17 Similar to Rb functionSimilar to Rb function Dominant versus Dominant versus
recessive recessive Familial/de novo Familial/de novo
inheritance or inheritance or spontaneous mutationsspontaneous mutations
Schwann cells/ LOHSchwann cells/ LOH IsoformsIsoforms
http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
http://missinglink.ucsf.edu/lm/DermatologyGlossary/neurofibroma.html
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
Learning Learning disabilities disabilities
http://www.sciencedaily.com/releases/2005/11/051111103003.htm
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
Learning Learning disabilities disabilities
Skeletal Skeletal abnormalitiesabnormalities
http://www.espine.com/adolescent-scoliosis.htm
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
Learning Learning disabilities disabilities
Skeletal Skeletal abnormalitiesabnormalities
Skin discolorationSkin discoloration
http://purplemoongarden.wordpress.com/2006/02/18/neurofibromatosis-type-1-life-with-tumors-lumpies-nubbies-bumpies-and-nodules/
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
Learning Learning disabilities disabilities
Skeletal Skeletal abnormalitiesabnormalities
Skin discolorationSkin discoloration Lisch nodulesLisch nodules
http://www.emedicine.com/oph/images/33210Lisch_Nodule_Clinical.jpg
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Neurofibromatosis Neurofibromatosis
Predisposition to Predisposition to nervous system nervous system tumorstumors
Learning Learning disabilities disabilities
Skeletal Skeletal abnormalitiesabnormalities
Skin discolorationSkin discoloration Lisch nodulesLisch nodules Optic nerve tumorsOptic nerve tumors
http://moon.ouhsc.edu/kfung/jty1/Com04/Com04Image/Com412-1-06.gif
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NF1 and CancerNF1 and Cancer
Nervous system Nervous system tumorstumors
Harrisingh & Lloyd Fig. 1
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NF1 and CancerNF1 and Cancer
Nervous system Nervous system tumorstumors
Neurofibroma Neurofibroma versus plexiform versus plexiform neurofibromneurofibrom
Harrisingh & Lloyd Fig. 1
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NF1 and CancerNF1 and Cancer
Nervous system Nervous system tumorstumors
Neurofibroma Neurofibroma versus plexiform versus plexiform neurofibromneurofibrom
Malignant Malignant Peripheral Nerve Peripheral Nerve Sheath TumorSheath Tumor
Harrisingh & Lloyd Fig. 1
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NF1 and CancerNF1 and Cancer
Nervous system Nervous system tumorstumors
Neurofibroma Neurofibroma versus plexiform versus plexiform neurofibromneurofibrom
Malignant Peripheral Malignant Peripheral Nerve Sheath TumorNerve Sheath Tumor
Multiple mutations Multiple mutations involvedinvolved
Harrisingh & Lloyd Fig. 1
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TreatmentsTreatments
SurgerySurgery Back BracesBack Braces RadiationRadiation ChemotherapyChemotherapy
http://www.wramc.army.mil/departments/Ortho/Ortho1/Images/Back_brace.jpg
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QUESTIONSQUESTIONS