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NEUROFIBROMATOSIS

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NEUROFIBRROMATOSIS

• Neurofbromatosis type 1 is a classic singlegene !isor!er "it# a#ig# rate o$ ne" mutations%

•  T#e NF1 gene is locate! on c#romosome 1&%

•  T#e protein pro!uct' neurofbromin' consists o$ ()1) aminoaci!s%

• *rotein inclu!es a !omain "it# guanosine trip#osp#atase+,T*ase-.acti/ating protein +,A*- $unction%

• Neurofbromin ,A* regulates con/ersion o$ Ras.guanosinetrip#osp#ate +,T*- to Ras.guanosine !ip#osp#ate +,0*-%

• NF1 gene mutations are #ig#ly !i/erse an! are $oun!t#roug#out t#e gene%

• Most mutations lea! to lac o$ e2pression o$ t#e gene pro!uct%

• Fe" genotype.p#enotype correlations are no"n' alt#oug#complete gene !eletions lea! to se/ere !isease%

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• 3oss o$ $unction o$ bot# NF1 alleles in Sc#"ann cells o$neurofbromas in!icates t#at NF1 $unctions as a tumorsuppressor gene%

• Neurofbromas consist o$ Sc#"ann cells "it# bot# NF1

alleles• mutate!' along "it# #etero4ygous fbroblasts' perineurial

cells' an! mast cells%

• Malignant tumors re5uire loss o$ NF1 $unction' as "ell asa!!itional genetic c#anges%

• *at#op#ysiology o$ nontumor mani$estations is unno"n6• NF1 #aploinsu7ciency may play a role%

• Mo!i$ying genes probably contribute to /ariable e2pression

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NF1 ,ene

•  Terleta pa!a romosom 1&511%(

•  Ter!apat 89:b 0NA' ;: eson

•

)<9& bp menyan!ian proteinneurofbromin  ()1) asam amino

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NF1 ,ene

• NF1 geneenco!es neurofbromin' negati/e regulator o$cellular proli$eration an! !i=erentiation%

• Neurofbromin inclu!es a guanosine trip#osp#atase +,T*ase-.acti/ating protein +,A*-

• Neurofbromin is e2presse! in neurons' glial cells' an! Sc#"anncells

•  T#e target o$ neurofbromin ,A* acti/ity is t#e intracellular signaltrans!ucer protein Ras%

• Ras is acti/ate! "#en certain cell sur$ace receptors' inclu!ingt#ose "it# tyrosine inase acti/ity' bin! ligan!%

• Ras is acti/ate! by a $amily o$ e2c#ange $actors an! is inacti/ate!by a $amily o$ proteins no"n as ,A*s  NEUROFIBRMIN

• Acti/ate! Ras interacts "it# an! alters t#e acti/ity o$ se/erale=ector proteins' lea!ing to /arious cellular responses' inclu!ingc#anges in gene e2pression

•

 T#e ,A*s stimulate a ,T*ase acti/ity intrinsic to Ras

 inacti/atet#e signal trans!uction con/erting Ras. ,T* to Ras. ,0*%

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>E,ANASAN

•  Ter?a!i arena !elesi besar besaranpa!a gen NF1

•  @uga ter!apat peran gen p98

• A!a ?uga yang mengataan ba#"a!elesi !i romosom 1: gen *TEN

 ?uga memilii peran !alamperembangan tumor men?a!i ganas

• >romosom 1: gen *TEN  Meng#ambat ter?a!inya eganasan

pa!a gen NF1