Gilles de la Tourette

Gilles de la Tourette

, PhD, DABMG

Tourette Syndrome GeneticsThe Southern and Eastern

Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette (GTS)

GTS

GTS ~10%

~15%

~12%

~35-40%

10-15%

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette (GTS)

GTS

: 53%

: 8%

: 77%

: 23%

Price et al. Arch Gen Psychiatry 1985Hyde et al. Neurology 1992

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

GTS, CT ( ) OC ( )

GTS

0.3740.3680.38

0.1150.1520.072OCB

0.1730.1680.175CT

0.0870.0340.15GTS

Pauls et al. Am J Hum Genet 1991

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette

(

)

GTSPauls and Leckman 1986, Pauls et al. 1991

Eapen et al. 1993, Van de Wetering 1993Hasstedt et al. 1995, Walkup et al. 1996

Hebebrand et al. 1997, Seuchter et al. 2000

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

(candidate gene approach)

(positional cloning)

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

(Single Nucleotide polymorphisms - SNPs)

( - -

(microsatellites STRPs)

1

2

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

1 1

1 2

1 1

1 1

2 2

1 1 2 2

2 2

1 2

1 12 2 1 2

2 22 2

2 21 2 1 2 1 2 1 1

1 2 1 2 1 2 2 2

2 2

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

GTS

DRD1, DRD2, DRD3, DRD4, DRD5(Grice et al. 1996, Comings et al. 1997, Lee et al. 2005 ..)

(DAT1)(Comings et al 1996, Faraone et al. 2005, Yoon et al. 2007 ..) (-)(Gade et al.1998, Daz-Anzalda et al. 2004 ..)

(5HTT)(Comings et al. 2001, Cheon et al. 2004 ..) -2 (TPH2) (Mssner et al 2007) (-)(Gade et al.1998, Daz-Anzalda et al. 2004 ..)

ADRA2A, ADRA2C(Xu et al. 2003 ..)

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

2p265 18

TSAICG 2006

17q254 96

Paschou et al. 2004

5, 10, 131 Curtis et al. 2004

2p, 8q, 11q Simonic et al. 2001

11q1

Merette et al. 20004q, 8p92 TSAICG 19995, 198 Barr et al. 1999

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

17q25 GTS

Utah (Leppert et al. 1996)

GTS (Zhang et al. 2002)

Zhang et al. Am J Hum Genet 2002

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

17q25 GTS

4 ( 462 105 GTS)

13 17 17 (17q25) 25 SNPs 17q25

96 ( GTS )

Paschou et al. Am J Hum Genet 2004

17q25

D17S928

Paschou et al. Am J Hum Genet 2004

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

25 SNPs 17q25

(Kb)

4 GTS

96 - GTS

- TDT (P

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

GTS

Taylor et al. 2001 9 Brett et al. 1996 - 3 8 Comings et al. 1996 - - 7 18 Petek et al. 2001 7q IMMP2L Crawford et al. 2003 - 6 8 State et al. 2003 18q21-q22 Verkerk et al. 2003 - 7 2 - CNTNAP2 Abelson et al. 2005 13q SLITRK1

,

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

SLITRK1

Slit and Trk-like 1 (SLITRK1) GTS

13q31.1 GTS.

Abelson et al. Science 2005

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

SLITRK1

174

.

3600 .

Abelson et al. Science 2005

mRNA SLITRK1 GTS. SLITRK1, .

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

SLITRK1 GTS

1191 GTS 2382 ( )

Abelson et al (2005)

H 3

Scharf et al. Neurology 2008

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette Syndrome Association International

Consortium for Genetics

TSAICG Am J Hum Genet 2006

2040 265 18 ( 272 - 91 GTS CT)

928 GTS CT311 OCD31 OCD

390 10 cM >80%

YGTSS, YBOCS, Conners, K-SADS-PL, SCID ()

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

TSAICG Am J Hum Genet 2006

390 2040 (928 GTS)

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

TSAICG Am J Hum Genet 2006

o 2p32.2

D2S144

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

2p

Verkerk et al. Genomics 2003

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette

Tourette Syndrome Association, USA

E GTS

GTS

GTS

GTS

( / )

(, , , , , , )

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette

GTS

600 (: GTS )

: 100 () GTS

http://utopia.duth.gr/~ppaschou/TSGeneSEE

http://tsgenesee.mbg.duth.gr

Tourette Syndrome Association, USA

Tourette Syndrome Genetics. The Southern and Eastern Europe Initiativehttp://tsgenesee.mbg.duth.gr/

Tourette

Tourette Syndrome Association, USA

ourette Syndrome Association International Consortium for Genetics

GTS

1 : 2.000 GTS ( )

2 : 4.000 GTS

500.000

( )

http://utopia.duth.gr/~ppaschou/TSGeneSEE tsgenesee@gmail.comhttp://tsgenesee.mbg.duth.gr

Tourette Syndrome Association, USA

/

Kenneth K. KiddJudith KiddAndrew PakstisJames LeckmanRobert KingYale University

David PaulsHarvard University

TSGeneSEE - http://tsgenesee.mbg.duth.gr/

Csaba Barta, Julia Gadoros, VadaskertTomasz Wolanczyk, Warsaw UniversityRenata Rizzo, University of Catania

Anatoly Severny, Moscow Res. Institute of PsychiatryVsevolod Rozanov, Odessa UniversityMira Kapisyzi, University Hospital Centre Mother Theresa