Anne Joutel - CADASIL, mechanisms of disease

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  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

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    NLIL^MH

    Dknglcmsds fb imsklsk

    Lcck @F[YKH

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    6

    ^DN/pkrmnytks

    rknkptfr dlhbucntmfc6

    >. Dknglcmsds fb Cftng>KNI/EFD ikpfsmts bfrdltmfc6

    9. Cfvkh bucntmfc elmcki ay dutlct Cftng>6

    Dknglcmsds fb NLIL^MH0 oky mssuks

    l-Cftng>KNI

  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

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    Alnoerfuci^trlmc(s)

    Cftng>

    kxprkssmfchkvkh

    Cftng>KNI

    / EFD

    Dmerlmck/

    N^I

    Ugmtk

    dlttkrhksmfcs

    Hlnuclr

    mcblrnts

    Dftfr /

    nfecmtmvkikbmnmts

    Dfusk (O-mc)Q

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    @futkh kt lh, @. Nhmc Mcvkst. 1:QKNI

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    [htrlstrunturlh nfrrkhltk fb mcmtmlh wgmtk dlttkr hksmfcs0

    mctrldykhmcmn fkikdl

    Nfeclt kt lh, mc prkplrltmfc

    K

    B

    Rlnufhks(%)

    Dykhmc-lssf

    nmltki

    vlnufhks(%)

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    ^knfcilry lxfclh ikekckrltmfc

    l-DAZl-CB

    Nfeclt kt lh, mc prkplrltmfc

  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

    7/35@futkh kt lh, @. Nhmc Mcvkst. 1:6

    Oky mssuks

    l-Cftng>KNI

    C t g> h o h m tg t t

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    QAZ@

    CMNI

    EYEEELL

    Cftng>

    Hmelcis

    (@leeki

    Lrtkrmlh dfrpgfekcksms (arlmc)

    Lrtkrmlh ^DN imbbkrkctmltmfc lci dlturltmfc

    Lrtkrmlh tfck

    Yrlcsnrmptmfclh lntmvltfr0 Cftng>, Ermp1,Crmp1, GkyH, Ov

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    Dfckt kt lh, GDE 1::

    Dfckt kt lh, Arlmc 1::=

    >9 KEBQ:

    ;

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    L

    A

    Nfeclt kt lh, suadmttk

    Ocfno-mc dmnk wmtg tgk lrngktyplh Lre m YeC>Q

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    3 Qkiunki Cftng> lntmvmty ms uchmokhy tgk irmvmce bfrnk mc NLIL^MH

    Nfeclt kt lh, suadmttk

    Khmdmcltmfc fb wmhitypk Cftng> mc YeC>Q

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    6^DN/pkrmnytks

    Ygk klrhmkst nkrkarfvlsnuhlr nglceks6

    Cftng> rknkptfr dlhbucntmfc6

    Dknglcmsds fb Cftng>KNI/EFD ikpfsmts bfrdltmfc6

    Cfvkh bucntmfc elmcki ay dutlct Cftng>6

    Oky mssuks

    l-Cftng>KNI

    C t g>KNI i mt m i i th b

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    QAZ@

    Cftng>

    Hmelcis

    (@leeki

    Cftng>KNI ikpfsmts fnnur mcikpkcikcthy fbhmelci lntmvltmfc fb tgk rknkptfr

    YegC>N917^,C>+/+ YegC>N917^,C>-/-YegC>UY,C>+/+

    N917^

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    l-Cftng>KNI

    ^DN

    Cftng>KNI ms l nfdpfckct fb EFD ikpfsmts

    @futkh kt lh, @NM 1:::

    Msgmof kt lh, Lntl Ckurfpltgfh 1::2

    Dfckt-Hkprtrk kt lh, Arlmc 1:

    Dutlct Cftng>KNI lnnuduhltks

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    Arlmc lrtkrmks

    QMZL1;,:::e

    Z

    ^

    L A

    hlkddhm+dk

    QMZL ^I^ 1%

    Cftng>KNI

    ^< ^1 ^>

    Clcf HN D^/D^

    Dutlct Cftng> lnnuduhltks

    mc imsuhbmik nrfss-hmcoki, iktkrekct-mcsfhuahk leerkeltks

    Dfckt-Hkprtrk kt lh, Arlmc 1: lnnuduhltks mc tgk arlmc vksskhs fb dfusk

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    YMDZ> lnnuduhltks mc tgk arlmc vksskhs fb dfuskdfikhs lci pltmkcts wmtg NLIL^MH

    L

    l-YMDZ>

    l-Cftng>

    kni

    l-^DL

    cfcYe YeC>Q

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    Rmtrfckntmc lacfrdlhhy ikpfsmts mc Cftng>

  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

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    YeCftng>UY

    YeCftng>Qkni dkrek

    l-Rtc l-C>kni dkrek

    l-Rtc

    a y pleerkeltks

    mc NLIL^MH arlmc vksskhs

    Dfckt-Hkprtrk kt lh, Arlmc 1:KNI prfdftks YMDZ>-Cftng>KNI

  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

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    L A N

    I

    Dfckt-Hkprtrk kt lh, Arlmc 1: prfdftks YMDZ> Cftng> mctkrlntmfc lci YMDZ> lnnuduhltmfc

    YMDZ-> mctkrlnts wmtg Rmtrfckntmc lci

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    L A

    Dfckt-Hkprtrk kt lh, Arlmc 1: mctkrlnts wmtg Rmtrfckntmc lci

    prfdftks Cftng>-Rmtrfckntmc nfdphkx bfrdltmfc

    Z i i h b C t g>KNI/EFD i mt b tm

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    () (9)

    YMDZ> Rmtrfckntmc FtgkrsDutlct Cftng>UY

    Zrfpfski dfikh bfr Cftng>KNI/EFD ikpfsmts bfrdltmfc

    O m

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    6^DN/pkrmnytks

    Ygk klrhy (pftkctmlhhy nlusltmvk) nkrkarfvlsnuhlr nglceks6

    Cftng> rknkptfr dlhbucntmfc6 Dknglcmsds fb Cftng>KNI/EFD ikpfsmts bfrdltmfc6

    Cfvkh bucntmfc elmcki ay dutlct Cftng>6

    Oky mssuks

    l-Cftng>KNI

    Ekckrlh prfpkrtmks fb tgk bfur Ymssuk mcgmamtfr

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    Ekckrlh prfpkrtmks fb tgk bfur Ymssuk mcgmamtfr

    dktlhhfprftkmclsks (YMDZs)

    Hfnltmfc DDZs mcgmamtki Ftgkr bucntmfcs Ekcktmnimsfrikr

    YMDZ< ^knrktki mc tgkKND

    Lhh DDZsLILD Afuci tf tgkKND

    Lhh DDZsLILD

  • 7/22/2019 Anne Joutel - CADASIL, mechanisms of disease

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    enkrkarfvlsnuhlr rkspfcsks

    L Acfc-Ye YeALN-YMDZ>(1)

    1:-oIl

    >:-oIl

    9:-oIl

    l-YMDZ>

    l-^DL:

    9

    ;

    2

    5

    7

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    YMDZ>prftkmchkv

    kh

    (bfhinglcek)

    YMDZ>

    Gud ALN

    9

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    kiun e > ksnuks nk ka f lsnu l

    iysbucntmfc mc YeCftng>Q, aut ckmtgkr fb YMDZ< cfr fb YMDZ1,

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    p , ,

    mdplmrs ckurfvlsnuhlr bucntmfc

    N. Nlpfck & L. @futk

    L

    rYMDZ1 tfpmnlh (

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    ( ) p

    iysbucntmfc mc YeYMDZ> lci YeCftng>Q

    LILDQKNI nlsnlik gypftgksms

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    Ygk Cftng>KNInlsnlik gypftgksms

    Nystkmck dutltmfc

    Cftng>KNI ikpfsmts

    Dltrmsfdk fb tgk ckurfvlsnuhlr ucmt(YMDZ>..)

    Nkrkarfvlsnuhlriysbucntmfc

    QkiuntmfcNlpmhhlry aki

    ^trunturlh lhtkrltmfcsArlmc lrtkrmks

    Kckrektmns/mfcmn gfdkfstlsms blmhurk

    NLIL^MH t 1:

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    LH[DCM

    A. Alrift (pfst-ifn), ^. Nhkfpglx (tkng ^tlbb), N. Iussluhk (D^n stuikct), Z. Blrifux(ZgI stuikct), N. Bfumhhlik (ZgI stuikct), Z. Hlnfdak (^nmkctmst), A. Hkdlmrk (tkng^tlbb), D. Dfckt-Hkprtrk (ZgI stuikct, pfst-ifn), D. Bfumhhft-Zlcngl (tkng ^tlbb), D.Qmlcm (D^n stuikct)

    NLIL^MH tkld- 1:

    Nfhhlafrltfrs

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    Nfhhlafrltfrs

    M Gliili & @. Rmcg (K^ZNM, Zlrms, Brlcnk)D. Nfgkc-Ylccfui`m & N. Alamckt+ (Zlstkur Mcstmtutk, Zlrms, Brlcnk)

    H Dksclri & K. Qfciklu (Mcskrd, Zlrms, Brlcnk)

    I. Gkcrmfc (Mcskrd, Lcekrs, Brlcnk)D Ikwkrngmc (RMA, Hkuvkc, Akhemud)N. Efskhk & C. Gackr (DIN Akrhmc, Ekrdlcy)

    N. Glbbckr & D. Imngelcs (Huiwme-Dlxmdmhmlcs-[cmvkrsmty, Ducmng, Ekrdlcy)G. ^tfkgr & A. Ukakr (Qkekcsaure [cmvkrsmty, Ekrdlcy)

    ^. Ngrmstkcskc, @. ^tlvkcglekc & @. Zkikrskc (Huciakno, Rlham, Ikcdlro)Y. Ermihky (@lnosfc Hla, Alr Glrafr, [^L)

    O. Yloldmyl & Q. Guelcmr (Ygk @fgcs Gfpomcs [cmvkrsmty ^ngffh fb Dkimnmck, Alhtmdfrk, [^L)B.Nkco Lyltl & D. Dfsofwmtz (Glrvlri Dkimnlh ^ngffh, Nglrhkstfwc, [^L)

    Ilakrtrlci & DY Ckhsfc ([cmvkrsmty fb Rkrdfct, Aurhmcetfc, [^L)

    Bucimce0 Cltmfclh Mcstmtutk Gklhtg (CMCI^), Kurfpklc Nfdducmty (Dlrmk Nurmk MYC), Lekcnk Cltmfclhkik hl Qkngkrngk, Bfciltmfc Hkiunq, G Huciakno L/^, Mcskrd, [cmvkrsmt Zlrms 5, Ems Dlhlimks Qlrks,Bfciltmfc pfur hl Qkngkrngk Dimnlhk, Birltmfc pfur hl Qkngkrngk pfur hk Nkrvklu

    Arlmc alcos 0 ^. Yuralct (EMK-CkurfNka, Zlrms), @@. Gluw (NG[ Zmtmk-^lhpktrmrk, Zlrms), B. Nglpfc(NG[ Nlkc), N. Efibrlmci (Nhmcmquk ^t Hun, Aruxkhhks, Akhemud), G. Olhmdf ([cmvkrsmty fb Yurou,Bmchlci), Y. Lrzakrekr (Arlmc Ckt, Ducmng, Ekrdlcy)Blnmhmtmks0 N. Dlrtmc (Yrlcsekcmn Dfusk blnmhmty, YLLD, Rmhhk`umb), N. Ygmaluht (DmnrfLrrly blnmhmty,

    MEADN, Mhhomrng), @.Z. Qmf (Khkntrfc dmnrfsnfpy blnmhmty, MBD, Zlrms)