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Gilles de la Tourette Syndrome Is Not Linked to D2-Dopamine Receptor

Gilles de la Tourette Syndrome Is Not Linked to D2-Dopamine Receptor Abstract • Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29,and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region. References 1. Bunzow JR, Van Tol HHM, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA . Nature . 1988;336:783-787.Crossref 2. Kurlan R, Behr J, Medved L, Shoulson I, Pauls D, Kidd JR, Kidd KK. Familial Tourette's syndrome: report of a large pedigree and potential for linkage analysis . Neurology . 1986;36:772-776.Crossref 3. Grandy DK, Litt M, Allen LJ, Bunzow J, Magenis RE, Civelli O. Dopamine D2 receptor gene maps to human chromosome 11q22-23 and identifies a Taq I RFLP . Cytogenet Cell Genet . 1989;51:1007. 4. Gelernter J, Grandy DK, Bunzow J, Pakstis AJ, Civelli O, Retief AI, Litt M, Kidd KK. D2 dopamine receptor locus (probe hD2G1) maps close to D11S29 (probe L7) and is also linked to PBGD (probe PBGD0.9) and D11S84 (probe p2-7-1D6) on 11q . Cytogenet Cell Genet . 1989;51:1002. 5. De Martinville B, Kunkel LM, Bruns G, Morlé F, Koenig M, Mandel JL, Horwich A, Latt SA, Gusella JF, Housman D, Francke U. Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus . Am J Hum Genet . 1985;37:235-249. 6. Zubrzycka-Gaarn EE, Bulman DE, Karpati G, Burghes AHM, Belfall B, Klamut HJ, Talbot J, Hodges RS, Ray PN, Worton RG. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle . Nature . 1988;333:466-469.Crossref 7. Kidd KK. Searching for major genes for psychiatric disorder . CIBA Found Symp . 1987;130:184-196. 8. Price RA, Kidd DK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome . Arch Gen Psychiatry . 1985;42:815-820.Crossref 9. Price RA, Leckman JF, Pauls DL, Cohen DJ, Kidd KK. Gilles de la Tourette's syndrome: tics and central nervous system stimulants in twins and nontwins . Neurology . 1986;36:232-237.Crossref 10. Nee LE, Caine ED, Polinsky RJ, Eldridge R, Ebert MH. Gilles de la Tourette syndrome: clinical and family study of 50 cases . Ann Neurol . 1980;7:41-49.Crossref 11. Nee LE, Polinsky RJ, Ebert MH. Tourette syndrome: clinical and family studies . Adv Neurol . 1982;35:291-295. 12. Kidd KK, Prusoff BA, Cohen DJ. Familial pattern of Gilles de la Tourette syndrome . Arch Gen Psychiatry . 1980;37:1336-1339.Crossref 13. Pauls DL, Cohen DJ, Heimbuch R, Detlor J, Kidd KK. Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics . Arch Gen Psychiatry . 1981;38:1091-1093.Crossref 14. Kondo K, Nomura Y. Tourette syndrome in Japan: etiologic considerations based on associated factors and familial clustering . Adv Neurol . 1982;35:271-276. 15. Montgomery MA, Clayton PJ, Friedhoff AJ. Psychiatric illness in Tourette syndrome patients and first-degree relatives . Adv Neurol . 1982;35:335-339. 16. Pauls DL, Towbin KE, Leckman JF, Zahner GEP, Cohen DJ. Gilles de la Tourette's syndrome and obsessive-compulsive disorder . Arch Gen Psychiatry . 1986;43:1180-1182.Crossref 17. Devor EJ. Complex segregation analysis of Gilles de la Tourette syndrome: further evidence for a major locus mode of transmission . Am J Hum Genet . 1984;36:704-709. 18. Comings DE, Comings BG, Devor EJ, Cloninger CR. Detection of major gene for Gilles de la Tourette syndrome . Am J Hum Genet . 1984;36:586-600. 19. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors . N Engl J Med . 1986;315:993-997.Crossref 20. Price RA, Pauls DL, Kruger SD, Caine ED. Family data support a dominant major gene for Tourette syndrome . Psychiatry Res . 1988;24:251-261.Crossref 21. Leckman JF, Riddle MA, Cohen DJ. Pathobiology of Tourette's syndrome . In: Cohen DJ, Bruun RD, Leckman JF, eds. Tourette's Syndrome and Tic Disorders: Clinical Understanding and Treatment . New York, NY: John Wiley & Sons Inc; 1988:103-118. 22. Cohen DJ, Shaywitz BA, Caparulo BK, Young JG, Bowers MB. Chronic, multiple tics of Gilles de la Tourette's disease: CSF acid monoamine metabolites after probenecid administration . Arch Gen Psychiatry . 1978;35:245-250.Crossref 23. Cohen DJ, Shaywitz BA, Young JG, Carbonari CM, Nathanson JA, Lieberman D, Bowers MB, Maas JW. Central biogenic amine metabolism in children with the syndrome of chronic multiple tics of Gilles de la Tourette: norepinephrine, serotonin, and dopamine . J Am Acad Child Psychiatry . 1979;18:320-341.Crossref 24. Butler IJ, Koslow SH, Siefert WE, Capriolo RM, Singer HS. Biogenic amine metabolism in Tourette syndrome . Ann Neurol . 1979;6:37-39.Crossref 25. Ross MS, Moldofsky H. A comparison of pimozide and haloperidol in the treatment of Gilles de la Tburette syndrome . Am J Psychiatry . 1978;135:585-587. 26. Shapiro E, Shapiro AK, Fulop G, Hubbard M, Mandeli J, Nordlie J, Phillips RA. Controlled study of haloperidol, pimozide, and placebo for the treatment of Gilles de la Tourette's syndrome . Arch Gen Psychiatry . 1989;46:722-730.Crossref 27. Uhr SB, Pruit B, Berger PA, Stahl SM. Case report of four patients with Tourette syndrome treated with Piquindone, a D2 receptor antagonist . J Clin Psychopharmacol . 1986;6:128-130.Crossref 28. Sweet RD, Bruun R, Shapiro AK, Shapiro E. Presynaptic catecholamine antagonists as treatment for Tourette syndrome: effects of alpha-methyl-paratyrosine and tetrabenazine . Arch Gen Psychiatry . 1976;31:857-861.Crossref 29. Jankovic J, Glaze DG, Frost JD. Effect of tetrabenazine on tics and sleep of Gilles de la Tourette's syndrome . Neurology . 1984;34:688-692.Crossref 30. Klawans HL, Falk DA, Nausieda PA, Weiner WJ. Gilles de la Tourette syndrome after long-term chlorpromazine therapy . Neurology . 1978;28:1064-1068.Crossref 31. Klawans HL, Nausieda PA, Goetz CC, Tanner CM, Weiner WJ. Tourette-like symptoms following chronic neuroleptic therapy . Adv Neurol . 1982;35:415-418. 32. Fog R, Pakkenberg H, Regeur L, Pakkenberg B. 'Tardive' Tourette syndrome in relation to long-term neuroleptic treatment of multiple tics . Adv Neurol . 1982;35:133-140. 33. Ott J. A computer program for linkage analysis of general human pedigrees . Am J Hum Genet . 1976;28:528-529. 34. Lathrop GM, Lalouel JM, Julier C, Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination . Am J Hum Genet . 1985;37:482-498. 35. Anderson MA, Gusella JF. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines . In Vitro . 1984;20:856-858.Crossref 36. Junien C, McBride OW. Report of the committee on the genetic constitution of chromosome 11 . Cytogenet Cell Genet . 1989;51:226-258.Crossref 37. Kidd KK, Bowcock AM, Schmidtke RK, Track RK, Ricciuti F, Hutchings G, Bale A, Pearson P, Willard HF. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms . Cytogenet Cell Genet . 1989;51:622-947.Crossref 38. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis . J Mol Biol . 1975;98:503-517.Crossref 39. O'Malley KL, Stone KR, Todd RD. Identification of a D2 receptor subtype which elevates intracellular calcium . Soc Neurosci Abstr . 1989;15:424. 40. Pauls DL, Pakstis AJ, Kurlan R, Kidd KK, Leckman JF, Cohen DJ, Kidd JR, Como P, Sparkes R. Segregation and linkage analysis of Gilles de la Tourette's syndrome and related disorders . J Am Acad Child Adolesc Psychiatry . In press. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

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Publisher
American Medical Association
Copyright
Copyright © 1990 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1990.01810230089014
Publisher site
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Abstract

Abstract • Gilles de la Tourette syndrome has an important genetic component; the pathophysiology of this disorder may involve the dopamine system. We tested a D2-dopamine receptor (locus DRD2, recognized by probe hD2G1) for genetic linkage with Gilles de la Tourette syndrome. Using a genetic linkage map of the region of DRD2 on the long arm of chromosome 11 and restriction fragment length polymorphism data from a total of four markers (DRD2 itself, D11S84, D11S29,and PBGD), we were able to exclude linkage of this candidate gene and Gilles de la Tourette syndrome in two extended kindreds segregating for Gilles de la Tourette syndrome. This rules out causation of Gilles de la Tourette syndrome by mutation in DRD2 in the kindreds studied under the genetic assumptions we employed; use of the map and multipoint linkage analyses also allowed us to exclude a Gilles de la Tourette syndrome susceptibility locus from a larger genetic region. References 1. Bunzow JR, Van Tol HHM, Grandy DK, Albert P, Salon J, Christie M, Machida CA, Neve KA, Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA . Nature . 1988;336:783-787.Crossref 2. Kurlan R, Behr J, Medved L, Shoulson I, Pauls D, Kidd JR, Kidd KK. Familial Tourette's syndrome: report of a large pedigree and potential for linkage analysis . Neurology . 1986;36:772-776.Crossref 3. Grandy DK, Litt M, Allen LJ, Bunzow J, Magenis RE, Civelli O. Dopamine D2 receptor gene maps to human chromosome 11q22-23 and identifies a Taq I RFLP . Cytogenet Cell Genet . 1989;51:1007. 4. Gelernter J, Grandy DK, Bunzow J, Pakstis AJ, Civelli O, Retief AI, Litt M, Kidd KK. D2 dopamine receptor locus (probe hD2G1) maps close to D11S29 (probe L7) and is also linked to PBGD (probe PBGD0.9) and D11S84 (probe p2-7-1D6) on 11q . Cytogenet Cell Genet . 1989;51:1002. 5. De Martinville B, Kunkel LM, Bruns G, Morlé F, Koenig M, Mandel JL, Horwich A, Latt SA, Gusella JF, Housman D, Francke U. Localization of DNA sequences in region Xp21 of the human X chromosome: search for molecular markers close to the Duchenne muscular dystrophy locus . Am J Hum Genet . 1985;37:235-249. 6. Zubrzycka-Gaarn EE, Bulman DE, Karpati G, Burghes AHM, Belfall B, Klamut HJ, Talbot J, Hodges RS, Ray PN, Worton RG. The Duchenne muscular dystrophy gene product is localized in sarcolemma of human skeletal muscle . Nature . 1988;333:466-469.Crossref 7. Kidd KK. Searching for major genes for psychiatric disorder . CIBA Found Symp . 1987;130:184-196. 8. Price RA, Kidd DK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome . Arch Gen Psychiatry . 1985;42:815-820.Crossref 9. Price RA, Leckman JF, Pauls DL, Cohen DJ, Kidd KK. Gilles de la Tourette's syndrome: tics and central nervous system stimulants in twins and nontwins . Neurology . 1986;36:232-237.Crossref 10. Nee LE, Caine ED, Polinsky RJ, Eldridge R, Ebert MH. Gilles de la Tourette syndrome: clinical and family study of 50 cases . Ann Neurol . 1980;7:41-49.Crossref 11. Nee LE, Polinsky RJ, Ebert MH. Tourette syndrome: clinical and family studies . Adv Neurol . 1982;35:291-295. 12. Kidd KK, Prusoff BA, Cohen DJ. Familial pattern of Gilles de la Tourette syndrome . Arch Gen Psychiatry . 1980;37:1336-1339.Crossref 13. Pauls DL, Cohen DJ, Heimbuch R, Detlor J, Kidd KK. Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics . Arch Gen Psychiatry . 1981;38:1091-1093.Crossref 14. Kondo K, Nomura Y. Tourette syndrome in Japan: etiologic considerations based on associated factors and familial clustering . Adv Neurol . 1982;35:271-276. 15. Montgomery MA, Clayton PJ, Friedhoff AJ. Psychiatric illness in Tourette syndrome patients and first-degree relatives . Adv Neurol . 1982;35:335-339. 16. Pauls DL, Towbin KE, Leckman JF, Zahner GEP, Cohen DJ. Gilles de la Tourette's syndrome and obsessive-compulsive disorder . Arch Gen Psychiatry . 1986;43:1180-1182.Crossref 17. Devor EJ. Complex segregation analysis of Gilles de la Tourette syndrome: further evidence for a major locus mode of transmission . Am J Hum Genet . 1984;36:704-709. 18. Comings DE, Comings BG, Devor EJ, Cloninger CR. Detection of major gene for Gilles de la Tourette syndrome . Am J Hum Genet . 1984;36:586-600. 19. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors . N Engl J Med . 1986;315:993-997.Crossref 20. Price RA, Pauls DL, Kruger SD, Caine ED. Family data support a dominant major gene for Tourette syndrome . Psychiatry Res . 1988;24:251-261.Crossref 21. Leckman JF, Riddle MA, Cohen DJ. Pathobiology of Tourette's syndrome . In: Cohen DJ, Bruun RD, Leckman JF, eds. Tourette's Syndrome and Tic Disorders: Clinical Understanding and Treatment . New York, NY: John Wiley & Sons Inc; 1988:103-118. 22. Cohen DJ, Shaywitz BA, Caparulo BK, Young JG, Bowers MB. Chronic, multiple tics of Gilles de la Tourette's disease: CSF acid monoamine metabolites after probenecid administration . Arch Gen Psychiatry . 1978;35:245-250.Crossref 23. Cohen DJ, Shaywitz BA, Young JG, Carbonari CM, Nathanson JA, Lieberman D, Bowers MB, Maas JW. Central biogenic amine metabolism in children with the syndrome of chronic multiple tics of Gilles de la Tourette: norepinephrine, serotonin, and dopamine . J Am Acad Child Psychiatry . 1979;18:320-341.Crossref 24. Butler IJ, Koslow SH, Siefert WE, Capriolo RM, Singer HS. Biogenic amine metabolism in Tourette syndrome . Ann Neurol . 1979;6:37-39.Crossref 25. Ross MS, Moldofsky H. A comparison of pimozide and haloperidol in the treatment of Gilles de la Tburette syndrome . Am J Psychiatry . 1978;135:585-587. 26. Shapiro E, Shapiro AK, Fulop G, Hubbard M, Mandeli J, Nordlie J, Phillips RA. Controlled study of haloperidol, pimozide, and placebo for the treatment of Gilles de la Tourette's syndrome . Arch Gen Psychiatry . 1989;46:722-730.Crossref 27. Uhr SB, Pruit B, Berger PA, Stahl SM. Case report of four patients with Tourette syndrome treated with Piquindone, a D2 receptor antagonist . J Clin Psychopharmacol . 1986;6:128-130.Crossref 28. Sweet RD, Bruun R, Shapiro AK, Shapiro E. Presynaptic catecholamine antagonists as treatment for Tourette syndrome: effects of alpha-methyl-paratyrosine and tetrabenazine . Arch Gen Psychiatry . 1976;31:857-861.Crossref 29. Jankovic J, Glaze DG, Frost JD. Effect of tetrabenazine on tics and sleep of Gilles de la Tourette's syndrome . Neurology . 1984;34:688-692.Crossref 30. Klawans HL, Falk DA, Nausieda PA, Weiner WJ. Gilles de la Tourette syndrome after long-term chlorpromazine therapy . Neurology . 1978;28:1064-1068.Crossref 31. Klawans HL, Nausieda PA, Goetz CC, Tanner CM, Weiner WJ. Tourette-like symptoms following chronic neuroleptic therapy . Adv Neurol . 1982;35:415-418. 32. Fog R, Pakkenberg H, Regeur L, Pakkenberg B. 'Tardive' Tourette syndrome in relation to long-term neuroleptic treatment of multiple tics . Adv Neurol . 1982;35:133-140. 33. Ott J. A computer program for linkage analysis of general human pedigrees . Am J Hum Genet . 1976;28:528-529. 34. Lathrop GM, Lalouel JM, Julier C, Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination . Am J Hum Genet . 1985;37:482-498. 35. Anderson MA, Gusella JF. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines . In Vitro . 1984;20:856-858.Crossref 36. Junien C, McBride OW. Report of the committee on the genetic constitution of chromosome 11 . Cytogenet Cell Genet . 1989;51:226-258.Crossref 37. Kidd KK, Bowcock AM, Schmidtke RK, Track RK, Ricciuti F, Hutchings G, Bale A, Pearson P, Willard HF. Report of the DNA committee and catalogs of cloned and mapped genes and DNA polymorphisms . Cytogenet Cell Genet . 1989;51:622-947.Crossref 38. Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis . J Mol Biol . 1975;98:503-517.Crossref 39. O'Malley KL, Stone KR, Todd RD. Identification of a D2 receptor subtype which elevates intracellular calcium . Soc Neurosci Abstr . 1989;15:424. 40. Pauls DL, Pakstis AJ, Kurlan R, Kidd KK, Leckman JF, Cohen DJ, Kidd JR, Como P, Sparkes R. Segregation and linkage analysis of Gilles de la Tourette's syndrome and related disorders . J Am Acad Child Adolesc Psychiatry . In press.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Nov 1, 1990

References

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