Neurofibromatosis 1Neurofibromatosis 1

Valerie KhodushValerie Khodush

March 27, 2007March 27, 2007

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

Remember RasRemember Ras

Gilbert Fig. 6.14

NF1 is a Ras-GapNF1 is a Ras-Gap

http://www.charite.de/ch/medgen/eumedis/embryology04/neurocutan-disorders/Slide4.png

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

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+/-)

Neurofibromin Neurofibromin

Chromosome 17Chromosome 17

http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg

Neurofibromin Neurofibromin

Chromosome 17Chromosome 17 Similar to Rb Similar to Rb

functionfunction

http://ghr.nlm.nih.gov/dynamicImages/chromomap/nf1.jpeg

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

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

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

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

Neurofibromatosis Neurofibromatosis

Predisposition to Predisposition to nervous system nervous system tumorstumors

http://missinglink.ucsf.edu/lm/DermatologyGlossary/neurofibroma.html

Neurofibromatosis Neurofibromatosis

Predisposition to Predisposition to nervous system nervous system tumorstumors

Learning Learning disabilities disabilities

http://www.sciencedaily.com/releases/2005/11/051111103003.htm

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

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/

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

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

NF1 and CancerNF1 and Cancer

Nervous system Nervous system tumorstumors

Harrisingh & Lloyd Fig. 1

NF1 and CancerNF1 and Cancer

Nervous system Nervous system tumorstumors

Neurofibroma Neurofibroma versus plexiform versus plexiform neurofibromneurofibrom

Harrisingh & Lloyd Fig. 1

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

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

TreatmentsTreatments

SurgerySurgery Back BracesBack Braces RadiationRadiation ChemotherapyChemotherapy

http://www.wramc.army.mil/departments/Ortho/Ortho1/Images/Back_brace.jpg

QUESTIONSQUESTIONS