Velázquez-Pérez L, Hernández-Hernández O, Leyva-García N, Cortés H, Cisneros B, Magaña JJ

Language: Spanish
References: 53
Page: 114-122
PDF size: 220.10 Kb.

ABSTRACT

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant genetic disease characterized by cerebellar dysfunction associated with slow saccades, early hyporeflexia, severe tremor of postural or action type, peripheral neuropathy, cognitive disorders, and other multisystemic features. Currently SCA2 is considered one of the most common ataxias worldwide. SCA2 is a polyglutamine disease caused by the abnormal expansion of CAG triplet repeat located in the ATXN2 gene. Affected individuals carry more than 32 and up to several hundred of CAG repeats. In this review we present a detailed description of epidemiology, clinical, genetic, electrophysiological and neuropathological characteristics of SCA2. The experience in applying early molecular diagnosis and a predictive diagnosis program in Cuba have allowed the establishment of rehabilitation programs for patients with SCA2.

REFERENCES

1. Manto MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005; 4: 2-6.

2. Harding AE. The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the drew family of Walworth. Brain. 1982; 105: 1-28.

3. Matilla-Dueñas A, Corral-Juan M, Volpini V, Sanchez I. The spinocerebellar ataxias: clinical aspects and molecular genetics. Adv Exp Med Biol. 2012; 724: 351-374.

4. Ellegren H. Heterogeneous mutation processes in human microsatellite DNA sequences. Nat Genet. 2000; 24: 400-402.

5. Pearson CE, Nichol-Edamura K, Cleary JD. Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet. 2005; 6: 729-742.

6. Velázquez-Pérez L, Cruz GS, Santos-Falcón N, Enrique Almaguer Mederos L, Escalona Batallan K, Rodríguez Labrada R et al. Molecular epidemiology of spinocerebellar ataxias in Cuba: Insights into SCA2 founder effect in Holguin. Neurosci Lett. 2009; 454: 157-160.

7. Saleem Q, Choudhry S, Mukerji M, Bashyam L, Padma MV, Chakravarthy A 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.

8. Velázquez-Pérez L, García R, Santos FN, Paneque HM, Medina HE, Hechavarría PR. Epidemiology of Cuban hereditary ataxias. Rev Neurol. 2001; 32: 606-611.

9. Alonso E, Martínez-Ruano L, DeBiase I, Mader C, Ochoa A, Yescas P et al. Distinct distribution of autosomal dominant spinocerebellar ataxia in the Mexican population. Mov Disord. 2007; 22: 1050-1053.

10. Magaña JJ, Tapia-Guerrero YS, Velázquez-Pérez L, Cerecedo-Zapata CM, Maldonado-Rodríguez M, Jano-Ito J et al. Analysis of CAG repeats in five SCA loci in Mexican population: Epidemiological evidence of a SCA7 founder effect. Clin Genet. 2014; 85: 159-165.

11. Magaña JJ, Vergara MD, Sierra-Martínez M, García-Jiménez E, Rodríguez-Antonio F, Gómez M del R et al. Molecular analysis of the CAG repeat among patients with Type-2 spinocerebellar ataxia in the Mexican population. Gac Med Mex. 2008; 144: 413-418.

12. Wadia NH, Swami RK. A new form of heredo-familiar spinocerebellar degeneration with slow eye movements (nine families). Brain. 1971; 94: 359-374.

13. Velázquez-Pérez L, Seifried C, Santos-Falcón N, Abele M, Ziemann U, Almaguer LE et al. Saccade velocity is controlled by polyglutamine size in spinocerebellar ataxia 2. Ann Neurol. 2004; 56: 444-447.

14. Velázquez-Pérez L, Seifried C, Abele M, Wirjatijasa F, Rodríguez-Labrada R, Santos-Falcón N et al. Saccade velocity is reduced in presymptomatic spinocerebelar ataxia type 2. Clin Neurophysiol. 2009; 120: 632-635.

15. Velázquez Pérez L, Sanchez Cruz G, Canales Ochoa N, Rodríguez Labrada R, Rodríguez Díaz J, Almaguer Mederos L et al. Electrophysiological features in patients and presymptomatic relatives with spinocerebellar ataxia type 2. J Neurol Sci. 2007; 263: 158-164.

16. Velázquez-Pérez L, Rodríguez-Labrada R, Canales-Ochoa N, Sánchez-Cruz G, Fernández-Ruiz J, Montero JM et al. Progression markers of Spinocerebellar ataxia 2. A twenty years neurophysiological follow up study. J Neurol Sci. 2010; 290: 22-26.

17. Rodríguez-Labrada R, Velázquez-Pérez L, Canales-Ochoa N, Galicia-Polo L, Haro-Valencia R, Sánchez-Cruz G et al. Subtle REM Sleep Abnormalities in presymptomatic spinocerebellar ataxia type 2 gene carriers. Mov Disord. 2011; 26: 347-350.

18. Velázquez-Pérez L, Rodríguez-Labrada R, García-Rodríguez JC, Almaguer-Mederos LE, Cruz-Mariño T, Laffita-Mesa JM. A Comprehensive review of spinocerebellar ataxia type 2 in Cuba. Cerebellum. 2011; 10 (2): 184-198.

19. Furtado S, Payami H, Lockhart PJ, Hanson M, Nutt JG, Singleton AA et al. Profile of families with parkinsonism predominant spinocerebellar ataxia type 2 (SCA2). Mov Disord. 2004; 19: 622-629.

20. Simon-Sánchez J, Hanson M, Singleton A, Hernández D, McInerney A, Nussbaum R et al. Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: evidence of SCA-2 expansion in a family with autosomal dominant Parkinson’s disease. Neurosci Lett. 2005; 382: 191-194.

21. Velázquez-Pérez L, Fernández-Ruiz J, Díaz R, González RP, Ochoa NC, Cruz GS et al. Spinocerebellar ataxia type 2 olfactory impairment shows a pattern similar to other major neurodegenerative diseases. J Neurol. 2006; 253: 1165-1169.

22. Reynaldo-Armiñán RD, Reynaldo-Hernández R, Paneque-Herrera M, Prieto-Avila L, Pérez-Ruiz E. Mental disorders in patients with spinocerebellar ataxia type 2 in Cuba. Rev Neurol. 2002; 35: 818-821.

23. Fernández-Ruiz J, Velázquez-Pérez L, Díaz R, Drucker-Colyn R, Pérez-González R, Canales BN. Prism adaptation in spinocerebellar ataxia type 2. Neuropsychologia. 2007; 45: 2692-2698.

24. Velázquez-Pérez L, Rodríguez-Labrada R, Canales-Ochoa N, Montero JM, Sánchez-Cruz G, Aguilera R et al. Progression of early features of spinocerebellar ataxia type 2 in individuals at risk: a longitudinal study. Lancet Neurol. 2014; 13 (5): 482-489.

25. Gierga K, Burk K, Bauer M, Orozco Díaz G, Auburger G, Schultz C et al. Involvement of the cranial nerves and their nuclei in spinocerebellar ataxia type 2 (SCA2). Acta Neuropathol. 2005; 109: 617-631.

26. Rub U, Del Turco D, Burk K, Díaz GO, Auburger G, Mittelbronn M et al. Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2. Neuropathol Appl Neurobiol. 2005; 31: 127-140.

27. Rub U, Seidel K, Ozerden I, Gierga K, Brunt ER, Schols L et al. Consistent affection of the central somatosensory system in spinocerebellar ataxia type 2 and type 3 and its significance for clinical symptoms and rehabilitative therapy. Brain Res Rev. 2007; 53: 235-249.

28. Ying SH, Choi SI, Lee M, Perlman SL, Baloh RW, Toga AW et al. Relative atrophy of the flocculus and ocular motor dysfunction in SCA2 and SCA6. Ann NY Acad Sci. 2005; 1039: 430-435.

29. Hoche F, Seidel K, Brunt ER, Auburger G, Schols L, Burk K et al. Involvement of the auditory brainstem system in spinocerebellar ataxia type 2 (SCA2), type 3 (SCA3) and type 7 (SCA7). Neuropathol Appl Neurobiol. 2008; 34: 479-491.

30. Rub U, Schultz C, Del Tredici K, Gierga K, Reifenberger G, de Vos RA et al. Anatomically based guidelines for systematic investigation of the central somatosensory system and their application to a spinocerebellar ataxia type 2 (SCA2) patient. Neuropathol Appl Neurobiol. 2003; 29: 418-433.

31. Huynh DP, Del Bigio MR, Ho DH, Pulst SM. Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer’s disease and spinocerebellar ataxia 2. Ann Neurol. 1999; 45: 232-241.

32. Sánchez-Cruz G, Velázquez-Pérez L, Gómez-Peña L, Martínez-Góngora E, Castellano-Sánchez G, Santos-Falcón N. Dysautonomic features in patients with Cuban type 2 spinocerebellar ataxia. Rev Neurol. 2001; 33: 428-434.

33. Tan EK, Ashisawa T. Genetic testing in spinocerebellar ataxias: Defining a clinical role. Arch Neurol. 2001; 58: 191-195.

34. Sanpei K, Takano H, Igarashi S, Sato T, Oyake M, Sasaki H et al. Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet. 1996; 14: 277-284.

35. Magaña JJ, Velázquez-Pérez L, Cisneros B. Spinocerebellar ataxia type 2: clinical presentation, molecular mechanisms, and therapeutic perspectives. Mol Neurobiol. 2013; 47: 90-104.

36. Sahba S, Nechiporuk A, Figueroa KP, Nechiporuk T, Pulst SM. Genomic structure of the Human Gene for spinocerebellar ataxia 2 (SCA2) on chromosome 12q24.1. Genomics. 1998; 47: 359-364.

37. Mao R, Aylsworth AS, Potter N, Wilson WG, Breningstall G, Wick MJ et al. Childhood-onset ataxia: testing for large CAG-repeats in SCA2 and SCA7. Am J Med Genet. 2002; 110: 338-345.

38. Andrés AM, Lao O, Soldevila M, Calafell F, Bertranpetit J. Dynamics of CAG repeat loci revealed by the analysis of their variability. Hum Mut. 2002; 21: 61-70.

39. Laffita-Mesa JM, Velázquez-Pérez LC, Santos Falcón N, Cruz-Mariño T, González Zaldívar Y, Vázquez Mojena Y et al. Unexpanded and intermediate CAG polymorphisms at the SCA2 locus (ATXN2) in the Cuban population: Evidence about the origin of expanded SCA2 alleles. Eur J Hum Genet. 2012; 20: 41-49.

40. Fernández M, McClain ME, Martínez RA, Snow K, Lipe H, Ravits J et al. Late-onset SCA2: 33 CAG repeats are sufficient to cause disease. Neurology. 2000; 55: 569-572.

41. Dorschner MO, Barden D, Stephens K. Diagnosis of five spinocerebellar ataxia disorders by multiplex amplification and capillary electrophoresis. J Mol Diagn. 2002; 4: 108-113.

42. Giunti P, Sabbadini G, Sweeney MG, Davis MB, Veneziano L, Mantuano E et al. The role of SCA2 trinucleotide repeat expansion in 89 autosomal dominant cerebellar ataxia families: frequency, clinical and genetics correlates. Brain. 1998; 121: 459-467.

43. Pulst SM, Santos N, Wang D, Yang H, Huynh D, Velázquez L et al. Spinocerebellar ataxia type 2: polyQ repeat variation in the CACNA1A calcium channel modifies age of onset. Brain. 2005; 128: 2297-2303.

44. Simon DK, Zheng K, Velázquez L, Figueroa KP, Falcon N, Almaguer LE, Pulst SM. Mithochondrial complex I gene variant associated with early age of onset in SCA2. Arch Neurol. 2007; 64: 1042-1044.

45. Hayes S, Turecki G, Brisebois K, Lopes-Cendes I, Gaspar C, Riess O et al. CAG repeat length in RAI1 is associated with age at onset variability in spinocerebellar ataxia type 2 (SCA2). Hum Mol Genet. 2000; 9: 1753-1758.

46. European Community Huntington Disease Collaborative Study Group. Ethical and social issues in presymptomatic testing for Huntington’s disease: A European Community collaborative study. J Med Genet. 1993; 30: 1028-1035.

47. Sequeiros J. Protocolo geral do Programa Nacional de Teste Preditivo e Aconselhamento Gen’etico na Doença de Machado-Joseph. In: Sequeiros J, ed. O Teste Preditivo da Doença de Machado-Joseph. Porto: UnIGene, IBMC; 1996. pp. 123-149.

48. Handyside A, Kontogianni E, Hardy K, Winston RM. Pregnancies from biopsied human preimplantation embryos sexed by Y-specific DNA amplification. Nature. 1990; 344: 768-770.

49. Moutou C, Nicod JC, Gardes N, Viville S. Birth after pre-implantation genetic diagnosis (PGD) of spinocerebellar ataxia 2 (Sca2). Prenat Diagn. 2008; 28 (2): 126-130.

50. Paneque HM, Prieto AL, Reynaldo RR, Cruz MT, Santos FN, Almaguer ML et al. Psychological Aspects of presymptomatic diagnosis of spinocerebellar ataxia type 2 in Cuba. Commun Genet. 2007; 10: 132-139.

51. Paneque HM, Lemos C, Escalona K, Prieto L, Reynaldo R, Velázquez M et al. Psychological follow-up of presymptomatic genetic testing for spinocerebellar ataxia type 2 (SCA2) in Cuba. J Genet Counsel 2007; 16: 469-479.

52. Cruz Mariño T, Velázquez Pérez L, González Zaldívar Y, Aguilera Rodríguez R, Velázquez Santos M, Vázquez Mojena Y et al. The Cuban Program for Predictive Testing of SCA2: 11 years and 768 individuals to learn from. Clin Genet. 2013; 83: 518-524.

53. Pérez-Ávila I, Fernández-Vieitez JA, Martínez-Góngora E, Ochoa-Mastrapa R, Velázquez-Manresa MG. Effects of a physical training program on quantitative neurological indices in mild stage type 2 spinocerebelar ataxia patients. Rev Neurol. 2004; 39: 907-910.