Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-26T23:15:23.131Z Has data issue: false hasContentIssue false
  • English
  • Français

Autosomal Dominant Spinocerebellar Ataxias: An Asian Perspective

Published online by Cambridge University Press:  02 December 2014

E.K. Tan
E.K. Tan*
Affiliation:
Department of Neurology, Singapore General Hospital, Singapore
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Autosomal dominant cerebellar ataxias, frequently referred to as spinocerebellar ataxias (SCAs) have been under intense scientific research limelight since expansions of coded CAG trinucleotide repeats were demonstrated to cause several dominantly inherited SCAs. The number of new SCA loci has expanded dramatically in recent years. At least ten genes have been identified for SCAs 1, 2, 3, 6, 7, 8, 10, 12, 17, dentatorubral-pallidoluysian atrophy (DRPLA), and six loci responsible for SCAs 4, 5, 11,13, 14, and 16 have been mapped. Genetic testing is essential for diagnosis due to the overlapping and varied phenotypic features of the different SCAs. While there is no effective treatment available, genetic counseling is important for addressing the many ethical, social, legal, and psychological issues facing SCA patients. Researchers have recently provided valuable information on the pathogenesis of the disease and hopefully a cure will be available in the near future.

Résumé:

RÉSUMÉ:

Les ataxies cérébelleuses autosomiques dominantes, souvent nommées ataxies spino-cérébelleuses (ASCs), ont suscité beaucoup d'intérêt dans le monde scientifique depuis la découverte qu'une expansion des répétitions du trinucléotide CAG est la cause de plusieurs ASCs dont l'hérédité est dominante. Le nombre de nouveaux loci ASC a augmenté rapidement dans les dernières années. Au moins dix gènes ont été identifiés pour les ASCs 1, 2, 3, 6, 7, 8, 10, 12, 17 et l'atrophie dentatorubro-pallidoluysienne (ADRPL) et six loci responsables des ASCs 4, 5, 11, 13, 14 et 16 ont été cartographiés. Le test génétique est essentiel au diagnostic parce que les caractéristiques phénotypiques des différentes ASCs sont variées et se recoupent. Bien qu'aucun traitement efficace ne soit disponible, le conseil génétique est important pour examiner les aspects éthiques, sociaux, légaux et psychologiques auxquels les patients sont confrontés. Les chercheurs ont fourni des informations précieuses sur la pathogenèse de la maladie et il est à espérer qu'un traitement soit bientôt disponible.

Type
Exchange Article
Information
Canadian Journal of Neurological Sciences , Volume 30 , Issue 4 , November 2003 , pp. 361 - 367
Copyright
Copyright © The Canadian Journal of Neurological 2003

References

1. Tan, EK, Ashizawa, T. Genetic testing in spinocerebellar ataxia: defining a clinical role. Arch Neurol 2001;58:191–195.CrossRefGoogle ScholarPubMed
2. Wells, RD, Warren, ST. Genetic instabilities and hereditary neurological diseases. Academic Press 1998.Google Scholar
3. Subramony, SH, Filla, A. Autosomal dominant spinocerebellar ataxias ad infinitum? Neurology 2001;56:287–289.Google Scholar
4. Klockgether, T, Wullner, U, Spauschus, A, Evert, B. The molecular biology of the autosomal dominant cerebellar ataxias. Mov Disord 2000;15:604–612.Google Scholar
5. Holmes, G. An attempt to classify cerebellar disease, with a note on Marie’s hereditary ataxia. Brain 1907;30:545–567.CrossRefGoogle Scholar
6. Harding, AE. Clinical features and classification of inherited ataxias. Adv Neurol 1993; 61:1–14.Google ScholarPubMed
7. Orr, HT, Chung, M, Banfi, S, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 1993;4:221–226.CrossRefGoogle ScholarPubMed
8. Pulst, SM, Nechiporuk, A, Nechiporuk, T, et al. Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nat Genet 1996;14:269–276.CrossRefGoogle ScholarPubMed
9. Imbert, G, Saudou, F, Yvert, G, et al Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 1996;14:285–291.Google Scholar
10. Geschwind, DH, Perlman, S, Figueroa, CP, Treiman, LJ, Pulst, SM. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet 1997;60: 842–850.Google Scholar
11. Kawaguchi, Y, Okamoto, T, Taniwaki, M, et al. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 1994;8:221–228.Google Scholar
12. Flanigan, K, Gardner, K, Alderson, K, et al. Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet 1996;59:392–399.Google Scholar
13. Ranum, LP, Schut, LJ, Lundgren, JK, Orr, HT, Livingston, DM. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet 1994;8:280–284.Google Scholar
14. Zhuchenko, O, Bailey, J, Bonnen, P, et al. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the alpha (1A)-voltage-dependent calcium channel. Nat Genet 1997;15:62–69.CrossRefGoogle ScholarPubMed
15. David, G, Abbas, N, Stevanin, G, et al. Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat Genet 1997;17: 65–70. Google Scholar
16. Koob, MD, Moseley, ML, Schut, LJ, et al. An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8). Nat Genet 1999;21:379–384.Google Scholar
17. Matsuura, T, Yamagata, T, Burgess, DL, et al. Large expansion of ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000;26:191–194.CrossRefGoogle ScholarPubMed
18. Worth, PF, Giunti, P, Gardner-Thorpe, C, et al. Autosomal dominant cerebellar ataxia type III: linkage in a large British family to a 7.6cM region on chromosome 15q14-21.3. Am J Hum Genet 1999;65:420–426.CrossRefGoogle Scholar
19. Holmes, SE, O’Hearn, EE, Mcinnis, MG, et al. Expansion of a novel CAG trinucleotide repeat in the 5’ region of PPP2R2B is associated with SCA12. Nat Genet 1999;23:391–392.CrossRefGoogle ScholarPubMed
20. Herman-Bert, A, Stevanin, G, Netter, J-C,et al. Mapping of spinocerebellar ataxia 13 to chromosome 19q13.3-q13.4 in a family with autosomal dominant cerebellar ataxia and mental retardation. Am J Hum Genet 2000;67:229–235.Google Scholar
21. Yamashita, I, Sasaki, H, Yabe, I, et al. A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. Ann Neurol 2000;48:156–163.Google Scholar
22. Miyoshi, Y, Yamada, T, Tanimura, M, et al. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology 2001;57:96–100.CrossRefGoogle ScholarPubMed
23. Nakamura, K, Jeong, SY, Uchihara, T, et al. SCA 17, a novel autosomal dominant cerebellar atxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 2001;10:1441–1448.Google Scholar
24. Browne, DL, Gancher, ST, Nutt, JG, et al. Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1. Nat Genet 1994;8:136–140.CrossRefGoogle ScholarPubMed
25. O phoff, RA, Terwindt, GM, Vergouwe, MN, et al. Familial hemiplegic migraine and episodic ataxia type-2 are caused by mutations in the Ca2+ channel gene CACNL1A4. Cell 1996;87:543–552.Google Scholar
26. Matsuura, T, Ranum, LP, Volpini, V, et al. Spinocerebellar ataxia type 10 is rare in populations other than Mexicans. Neurology 2002;58:983–984.Google Scholar
27. Higgins, JJ, Nee, LE, Vasconcelos, O, et al. Mutations in American families with spinocerebellar ataxia (SCA) type 3: SCA3 is allelic to Machado-Joseph disease. Neurology 1996;46:208–213.Google Scholar
28. Pareyson, D, Gellera, C, Castellotti, B, et al. Clinical and molecular studies of 73 Italian families with autosomal dominant cerebellar ataxia type I: SCA1 and SCA2 are the most common genotypes. J Neurol 1999;246:389–393.Google Scholar
29. Filla, A, De Michele, G, Santoro, L, et al. Spinocerebellar ataxia type 2 in southern Italy: a clinical and molecular study of 30 families. J Neurol 1999;246:467–471.CrossRefGoogle ScholarPubMed
30. Schols, L, Amoiridis, G, Epplen, JT, et al. Relations between genotype and phenotype in German patients with the Machado-Joseph disease mutation. J Neurol Neurosurg Psychiatry 1996;61:466–470.Google Scholar
31. Leggo, J, Dalton, A, Morrison, PJ,et al. Analysis of spinocerebellar ataxia types 1, 2, 3, and 6, dentatorubral-pallidoluysian atrophy, and Friedreich’s ataxia genes in spinocerebellar ataxia patients in the UK. J Med Genet 1997;34:982–985.Google Scholar
32. Mori, M, Adachi, Y, Kusumi, M, Nakashima, K. A genetic epidemiological study of spinocerebellar ataxias in Tottori prefecture, Japan. Neuroepidemiology 2001;20:144–149.Google Scholar
33. Mori, M, Adachi, Y, Kusumi, M, Nakashima, K. Spinocerebellar ataxia type 6: founder effect in Western Japan. J Neurol Sci 2001;185:43–47.CrossRefGoogle ScholarPubMed
34. Onodera, Y, Aoki, M, Tsuda, T, et al. High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan. J Neurol Sci 2000;178:153–158.Google Scholar
35. Yamashita, I, Sasaki, H, Yabe, I, et al. A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter. Ann Neurol 2000;48:156–163.Google Scholar
36. Sasaki, H, Yabe, I, Yamashita, I, Tashiro, K. Prevalence of triplet repeat expansion in ataxia patients from Hokkaido, the northernmost island of Japan. J Neurol Sci 2000;175:45–51.CrossRefGoogle ScholarPubMed
37. Ikeda, Y, Shizuka, M, Watanabe, M, Okamoto, K, Shoji, M. Molecular and clinical analyses of spinocerebellar ataxia type 8 in Japan. Neurology 2000;54:950–955.CrossRefGoogle ScholarPubMed
38. Seto, M, Tsujihata, M. Cluster of Machado-Joseph disease in a small rural town near Nagasaki City, Japan: clinical and genetic studies of two families. J Neurol 1999;246:405–407.Google Scholar
39. Shan, DE, Soong, BW, Sun, CM, et al. Spinocerebellar ataxia type 2 presenting as familial levodopa-responsive parkinsonism. Ann Neurol 2001;50:812–815.CrossRefGoogle ScholarPubMed
40. Soong, BW, Lu, YC, Choo, KB, Lee, HY. Frequency analysis of autosomal dominant cerebellar ataxias in Taiwanese patients and clinical and molecular characterization of spinocerebellar ataxia type 6. Arch Neurol 2001;58:1105–1109.Google Scholar
41. Zhou, YX, Qiao, WH, Gu, WH, et al. Spinocerebellar ataxia type 1 in China: molecular analysis and genotype-phenotype correlation in 5 families. Arch Neurol 2001;58:789–794.CrossRefGoogle Scholar
42. Gu, W, Wang, Y, Liu, X, et al. Molecular and clinical study of spinocerebellar ataxia type 7 in Chinese kindreds. Arch Neurol 2000;57:1513–1518.Google Scholar
43. Tang, B, Liu, C, Shen, L, et al. Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol 2000;57:540–554.Google Scholar
44. Cai, T, Yu, P, Chen, X, Lopa, M. Trinucleotide repeat expansion of spinocerebellar ataxia (SCA1) found in a Chinese family. Chin Med J (Engl) 1998;111:160–162.Google Scholar
45. Tang, B, Wang, D, Xia, J. SCA1, SCA2, MJD/SCA3 (CAG)n mutation detection and analysis in patients with hereditary spinocerebellar ataxia from Chinese families. Zhonghua Yi Xue Za Zhi 1997;77:819–822.Google Scholar
46. Zhou, YX, Wang, GX, Tang, BS, et al. Spinocerebellar ataxia type 2 in China: molecular analysis and genotype-phenotype correlation in nine families. Neurology 1998;51:595–598.Google Scholar
47. Hsieh, M, Tsai, HF, Lu, TM, et al. Studies of the CAG repeat in the Machado-Joseph disease gene in Taiwan. Hum Genet 1997;100:155–162.Google Scholar
48. Srivastava, AK, Choudhry, S, Gopinath, MS, et al. Molecular and clinical correlation in five Indian families with spinocerebellar ataxia 12. Ann Neurol 2001;50:796–800.Google Scholar
49. Gangopadhyay, PK, Ghosh, B, Roy, T, et al. Spinocerebellar ataxia-type 6. J Assoc Physicians India 2001;49:658–659.Google Scholar
50. Fujigasaki, H, Verma, IC, Camuzat, A, et al. SCA12 is a rare locus for autosomal dominant cerebellar ataxia: a study of an Indian family. Ann Neurol 2001;49:117–121.Google Scholar
51. Basu, P, Chattopadhyay, B, Gangopadhaya, PK, et al. Analysis of CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7 and DRPLA loci in spinocerebellar ataxia patients and distribution of CAG repeats at the SCA1, SCA2 and SCA6 loci in nine ethnic populations of eastern India. Hum Genet 2000;106:597–604.Google Scholar
52. Saleem, Q, Choudhry, S, Mukerji, M, et al. Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation. Hum Genet 2000;106:179–187.Google Scholar
53. Pang, J, Allotey, R, Wadia, N, et al. A common disease haplotype segregating in spinocerebellar ataxia 2 (SCA2) pedigrees of diverse ethnic origin. Eur J Hum Genet 1999;7(7):841–845.Google Scholar
54. Wadia, N, Pang, J, Desai, J, et al. A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis. Brain 1998;121(Pt 12):2341–2355.Google Scholar
55. Giunti, P, Sweeney, MG, Harding, AE. Detection of the Machado-Joseph disease/spinocerebellar ataxia three trinucleotide repeat expansion in families with autosomal dominant motor disorders, including the Drew family of Walworth. Brain 1995;118(Pt 5):1077–1085.Google Scholar
56. Koh, SH, Kim, HT, Kim, SH, et al. Spinocerebellar ataxia type 6 and episodic ataxia type 2 in a Korean family. J Korean Med Sci 2001;16:809–813.Google Scholar
57. Kim, JM, Shin, S, Kim, JY, et al. Spinocerebellar ataxia type 2 in seven Korean families: CAG trinucleotide expansion and clinical characteristics. J Korean Med Sci 1999;14:659–664.Google Scholar
58. Stevanin, G, David, G, Durr, A, et al. Multiple origins of the spinocerebellar ataxia 7 (SCA7) mutation revealed by linkage disequilibrium studies with closely flanking markers, including an intragenic polymorphism (G3145TG/A3145TG). Eur J Hum Genet 1999;7:889–896.Google Scholar
59. Jin, DK, Oh, MR, Song, SM, et al. Frequency of spinocerebellar ataxia types 1,2,3,6,7 and dentatorubral pallidoluysian atrophy mutations in Korean patients with spinocerebellar ataxia. J Neurol 1999;246:207–210.CrossRefGoogle Scholar
60. Tan, EK, Law, HY, Zhao, Y, et al. Spinocerebellar ataxias in Singapore: predictive features of a positive DNAtest? Eur Neurol 2000;44:168–171.Google Scholar
61. Monckton, DG, Cayuela, ML, Gould, FK, et al. Very large (CAG)(n) DNA repeat expansions in the sperm of two spinocerebellar ataxia type 7 males. Hum Mol Genet 1999;8:2473–2478.Google Scholar
62. Zoghbi, HY, Orr, HT. Polyglutamine diseases: protein cleavage and aggregation. Curr Opin Neurobiol 1999;9:566–570.Google Scholar
63. Cummings, CJ, Orr, HT, Zoghbi, HY. Progress in pathogenesis of spinocerebellar ataxia type 1. Philos Trans R Soc Lond 1999;354:1079–1081.CrossRefGoogle ScholarPubMed
64. Burright, EN, Davidson, JD, Duvick, LA, Koshy, B, Zoghbi, HY. Identification of a self-associated region within the SCA 1 gene product, ataxin-1. Hum Mol Genet 1997;6:513–518.CrossRefGoogle Scholar
65. Holmberg, M, Duyckaerts, C, Durr, A, et al. Spinocerebellar ataxia type 7 (SCA 7): a neurodegenerative disorder with neuronal intranuclear inclusions. Hum Mol Genet 1998;7:913–918.CrossRefGoogle Scholar
66. Paulson, HL, Perez, MK, Trottier, Y, et al. Intranuclear inclusions of expanded glutamine protein in spinocerebellar ataxia type 3. Neuron 1997;19:333–344.CrossRefGoogle ScholarPubMed
67. Skinner, PJ, Koshy, BT, Cummings, CJ, et al. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature 1997;389:971–974.Google Scholar
68. Cummings, CJ, Mancini, MA, Antalffy, B, et al. Chaperone suppression of aggregation and altered subcellular proteosome localization imply protein misfolding in SCA 1. Nat Genet 1998;19:148–154.Google Scholar
69. Chai, Y, Koppenhafer, SL, Shoesmith, SJ, Perez, MK, Paulson, HL. Evidence for proteosome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine in vitro. Hum Mol Genet 1999;8:673–682.Google Scholar
70. Klement, IA, Skinner, PJ, Kaytor, MD, et al. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induceddisease in SCA1 transgenic mice. Cell 1998;95:41–53.Google Scholar
71. Tan, EK, Lim, SH, Chan, LL, Wong, MC, Tan, KP. X-linked adrenoleukodystrophy: spinocerebellar variant. Clin Neurol Neurosurg 1999;101:137–140.Google Scholar
72. Guidelines for the molecular genetics predictive test in Huntington’s disease. International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington’s chorea. Neurology 1994;44:1533–1536.Google Scholar
73. Botez, MI, Botez-Marquard, T, Mayer, P, et al. The treatment of spinocerebellar ataxias: facts and hypotheses. Med Hypotheses 1998; 51:381–384.CrossRefGoogle Scholar
74. Gasser, T, Bressman, S, Durr, A, et al. State of the art review:molecular diagnosis of inherited movement disorders. Movement Disorders Society task force on molecular diagnosis. Mov Disord. 2003;18(1):3–18.Google Scholar