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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
7/22/2019 Anne Joutel - CADASIL, mechanisms of disease
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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
7/22/2019 Anne Joutel - CADASIL, mechanisms of disease
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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>
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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
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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
cfc-Ye YeALN-YMDZ>
YMDZ>prftkmchkv
kh
(bfhinglcek)
YMDZ>
Gud ALN
9
7/22/2019 Anne Joutel - CADASIL, mechanisms of disease
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kiun e > ksnuks nk ka f lsnu l
iysbucntmfc mc YeCftng>Q, aut ckmtgkr fb YMDZ< cfr fb YMDZ1,
7/22/2019 Anne Joutel - CADASIL, mechanisms of disease
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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:
7/22/2019 Anne Joutel - CADASIL, mechanisms of disease
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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)