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Ataxias with Autosomal, X-Chromosomal or Maternal Inheritance

Published online by Cambridge University Press:  02 December 2014

Josef Finsterer
Josef Finsterer*
Affiliation:
Krankenanstalt Rudolfstiftung, Vienna, Austria, Europe
*
Postfach 20, 1180 Vienna, Austria, Europe
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Abstract

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Heredoataxias are a group of genetic disorders with a cerebellar syndrome as the leading clinical manifestation. The current classification distinguishes heredoataxias according to the trait of inheritance into autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias. The autosomal dominant heredoataxias are separated into spinocerebellar ataxias (SCA1-8, 10-15, 17-23, 25-30, and dentato-rubro-pallido-luysian atrophy), episodic ataxias (EA1-7), and autosomal dominant mitochondrial heredoataxias (Leigh syndrome, MIRAS, ADOAD, and AD-CPEO). The autosomal recessive ataxias are separated into Friedreich ataxia, ataxia due to vitamin E deficiency, ataxia due to Abeta-lipoproteinemia, Refsum disease, late-onset Tay-Sachs disease, cerebrotendineous xanthomatosis, spinocerebellar ataxia with axonal neuropathy, ataxia telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia 1 and 2, spastic ataxia of Charlevoix-Saguenay, Cayman ataxia, Marinesco-Sjögren syndrome, and autosomal recessive mitochondrial ataxias (AR-CPEO, SANDO, SCAE, AHS, IOSCA, MEMSA, LBSL CoQ-deficiency, PDC-deficiency). Only two of the heredoataxias, fragile X/tremor/ataxia syndrome, and XLSA/A are transmitted via an X-linked trait. Maternally inherited heredoataxias are due to point mutations in genes encoding for tRNAs, rRNAs, respiratory chain subunits or single large scale deletions/duplications of the mitochondrial DNA and include MELAS, MERRF, KSS, PS, MILS, NARP, and non-syndromic mitochondrial disorders. Treatment of heredoataxias is symptomatic and supportive and may have a beneficial effect in single patients.

**Please see page 424 for abbreviation list.

Résumé:

RÉSUMÉ:

Les ataxies héréditaires regroupent des maladies génétiques dont la principale manifestation clinique est un syndrome cérébelleux. La classification actuelle de ces ataxies est basée sur le mode d’hérédité, soit autosomique dominant, autosomique récessif, lié à l’X et maternel. Les ataxies héréditaires autosomiques dominantes sont divisées en ataxies spinocérébelleuses (SCA1-8, 10-15, 17-23, 25-30 et atrophie dentato-rubro-pallido-luysienne), ataxies épisodiques (EA1-7) et ataxies héréditaires autosomiques dominantes mitochondriales (syndrome de Leigh, MIRAS, ADOAD et AD-CPEO). Les ataxies autosomiques récessives sont l’ataxie de Friedreich, l’ataxie due à un déficit en vitamine E, l’ataxie due à l’abêta-lipoprotéinémie, la maladie de Refsum, la maladie de Tay-Sachs à début tardif, la xanthomatose cérébrotendineuse, l’ataxie spinocérébelleuse avec neuropathie axonale, l’ataxie télangiectasie, l’ataxie ressemblant à l’ataxie télangiectasie, l’ataxie avec apraxie oculomotrice 1 et 2, l’ataxie spastique de Charlevoix-Saguenay, l’ataxie des îles Caïman, le syndrome deMarinesco- Sjögren et les ataxies mitochondriales autosomiques récessives (AR-CPEO, SANDO, SCAE, AHS, IOSCA, MEMSA, LBSL déficit en coenzyme Q, déficit en PDC). Seulement deux des ataxies héréditaires, le syndrome de l’X fragile/tremblement/ataxie et le XLSA/A ont un mode de transmission lié à l’X. Les ataxies héréditaires dont l’hérédité est maternelle sont dues à des mutations ponctuelles dans des gènes codant pour des ARNt, des ARNr, des sous-unités de la chaîne respiratoire ou des délétions/duplications uniques de grande taille de l’ADN mitochondrial dont MELAS, MERRF, KSS, PS,MILS, NARP et des maladies mitochondriales non syndromiques. Le traitement des ataxies héréditaires est un traitement symptomatique de soutien qui peut être bénéfique chez certains patients. **voir la page 424 pour la liste d’abrègement.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 36 , Issue 4 , July 2009 , pp. 409 - 428
Copyright
Copyright © The Canadian Journal of Neurological 2009

References

1. Fogel, BL, Perlman, S. Clinical features and molecular genetics of autosomal recessive cerebellar ataxias. Lancet Neurol. 2007;6: 245–57.CrossRefGoogle ScholarPubMed
2. Duenas, AM, Goold, R, Giunti, P. Molecular pathogenesis of spinocerebellar ataxias. Brain. 2006:129:1357–70.CrossRefGoogle ScholarPubMed
3. Pandolfo, M. Friedreich ataxia. Arch Neurol. 2008;65:1296–303.CrossRefGoogle ScholarPubMed
4. Honti, V, Vécsei, L. Genetic and molecular aspects of spinocerebellar ataxias. Neuropsychiatr Dis Treat. 2005;1:125–33.CrossRefGoogle ScholarPubMed
5. Tallaksen, CM. Hereditary ataxias. Tidsskr Nor Laegeforen. 2008;128:1977–80.Google ScholarPubMed
6. Manto, MU. The wide spectrum of spinocerebellar ataxias (SCAs). Cerebellum. 2005;4:2–6.CrossRefGoogle ScholarPubMed
7. Klockgether, T. The clinical diagnosis of autosomal dominant spinocerebellar ataxias. Cerebellum. 2008;7:101–5.CrossRefGoogle ScholarPubMed
8. van de Warrenburg, BP, Sinke, RJ, Verschuuren-Bemelmans, CC, Scheffer, H, Brunt, ER, Ippel, PF, et al. Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. Neurology. 2002;58:702–8.CrossRefGoogle ScholarPubMed
9. Tsuji, S, Onodera, O, Goto, J, Nishizawa, M: Study Group on Ataxic Diseases. Sporadic ataxias in Japan - a population-based epidemiological study. Cerebellum. 2008;7:189–97.CrossRefGoogle ScholarPubMed
10. Zortea, M, Armani, M, Pastorello, E, Nunez, GF, Lombardi, S, Tonello, S, et al. Prevalence of inherited ataxias in the province of Padua, Italy. Neuroepidemiology. 2004;23:275–80.CrossRefGoogle ScholarPubMed
11. Espinós-Armero, C, González-Cabo, P, Palau-Martínez, F. Autosomal recessive cerebellar ataxias. Their classification, genetic features and pathophysiology. Rev Neurol. 2005;41:409–22.Google ScholarPubMed
12. Koht, J, Tallaksen, CM. Cerebellar ataxia in the eastern and southern parts of Norway. Acta Neurol Scand Suppl. 2007;187:76–9.CrossRefGoogle ScholarPubMed
13. Brusco, A, Gellera, C, Cagnoli, C, Saluto, A, Castucci, A, Michielotto, C et al. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol. 2004;61:727–33.CrossRefGoogle ScholarPubMed
14. Sasaki, H, Yabe, I, Tashiro, K. The hereditary spinocerebellar ataxias in Japan. Cytogenet Genome Res. 2003;100:198–205.CrossRefGoogle ScholarPubMed
15. Jiang, H, Tang, BS, Xu, B, Zhao, GH, Shen, L, Tang, JG, et al. Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6. Chin Med J (Engl). 2005;118:837–43.Google ScholarPubMed
16. Zühlke, C, Bernard, V, Gillessen-Kaesbach, G. Investigation of recessive ataxia loci in patients with young age of onset. Neuropediatrics. 2007;38:207–9.CrossRefGoogle ScholarPubMed
17. Soong, BW, Paulson, HL. Spinocerebellar ataxias: an update. Curr Opin Neurol. 2007;20:438–46.CrossRefGoogle ScholarPubMed
18. Johnson, J, Wood, N, Giunti, P, Houlden, H. Clinical and genetic analysis of spinocerebellar ataxia type 11. Cerebellum. 2008;7:159–64.CrossRefGoogle ScholarPubMed
19. Storey, E, Bahlo, M, Fahey, MC, Sisson, O, Lueck, CJ, Gardner, RM. A new dominantly-inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry. 2008,(in press)CrossRefGoogle Scholar
20. Liu, CS, Cheng, WL, Kuo, SJ, Li, JY, Soong, BW, Wei, YH. Depletion of mitochondrial DNA in leukocytes of patients with poly-Q diseases. J Neurol Sci. 2008;264:18–21.CrossRefGoogle ScholarPubMed
21. Shao, J, Diamond, MI. Polyglutamine diseases: emerging concepts in pathogenesis and therapy. Hum Mol Genet. 2007;16(spec No. 2):R115–23.CrossRefGoogle ScholarPubMed
22. Netravathi, M, Pal, PK, Purushottam, M, Thennarasu, K, Mukherjee, M, Jain, S. Spinocerebellar ataxias types 1, 2 and 3: age adjusted clinical severity of disease at presentation correlates with size of CAG repeat lengths. J Neurol Sci. 2009;277:83–6.CrossRefGoogle ScholarPubMed
23. Nagai, Y, Popiel, HA, Fujikake, N, Toda, T. Therapeutic strategies for the polyglutamine diseases. Brain Nerve. 2007;59:393–404.Google ScholarPubMed
24. Safaei, S, Houshmand, M, Banoei, MM, Panahi, MS, Nafisi, S, Parivar, K et al. Mitochondrial tRNALeu/Lys and ATPase 6/8 gene variations in spinocerebellar ataxias. Neurodegener Dis. 2009;6:16–22.CrossRefGoogle ScholarPubMed
25. Döhlinger, S, Hauser, TK, Borkert, J, Luft, AR, Schulz, JB. Magnetic resonance imaging in spinocerebellar ataxias. Cerebellum. 2008;7:204–14.CrossRefGoogle ScholarPubMed
26. Garrard, P, Martin, NH, Giunti, P, Cipolotti, L. Cognitive and social cognitive functioning in spinocerebellar ataxia: a preliminary characterization. J Neurol. 2008;255:398–405.CrossRefGoogle ScholarPubMed
27. Matilla-Dueñas, A, Goold, R, Giunti, P. Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum. 2008;7:106–14.CrossRefGoogle ScholarPubMed
28. Globas, C, du Montcel, ST, Baliko, L, Boesch, S, Depondt, C, DiDonato, S, et al. Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6. Mov Disord. 2008;23:2232–8.CrossRefGoogle Scholar
29. Sasaki, H. Clinical feature and molecular genetics of hereditary spinocerebellar ataxia. Rinsho Shinkeigaku. 2007;47:795–800.Google ScholarPubMed
30. Rottnek, M, Riggio, S, Byne, W, Sano, M, Margolis, RL, Walker, RH. Schizophrenia in a patient with spinocerebellar ataxia 2: coincidence of two disorders or a neurodegenerative disease presenting with psychosis? Am J Psychiatry. 2008;165:964–7.CrossRefGoogle ScholarPubMed
31. Lastres-Becker, I, Rüb, U, Auburger, G. Spinocerebellar ataxia 2 (SCA2). Cerebellum. 2008;7:115–24.CrossRefGoogle ScholarPubMed
32. Rüb, U, Seidel, K, Ozerden, I, Gierga, K, Brunt, ER, Schöls, 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;53:235–49.CrossRefGoogle ScholarPubMed
33. Kim, JM, Hong, S, Kim, GP, Choi, YJ, Kim, YK, Park, SS, et al. Importance of low-range CAG expansion and CAA interruption in SCA2 Parkinsonism . Arch Neurol. 2007;64:1510–8.CrossRefGoogle ScholarPubMed
34. Hoche, F, Seidel, K, Brunt, ER, Auburger, G, Schöls, L, Bürk, 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;34:479–91.CrossRefGoogle ScholarPubMed
35. Armstrong, J, Bonaventura, I, Rojo, A, González, G, Corral, J, Nadal, N, et al. Spinocerebellar ataxia type 2 (SCA2) with white matter involvement. Neurosci Lett. 2005;381:247–51.CrossRefGoogle ScholarPubMed
36. Paulson, HL. Dominantly inherited ataxias: lessons learned from Machado-Joseph disease/spinocerebellar ataxia type 3. Semin Neurol. 2007;27:133–42.CrossRefGoogle ScholarPubMed
37. Riess, O, Rüb, U, Pastore, A, Bauer, P, Schöls, L. SCA3: neurological features, pathogenesis and animal models. Cerebellum. 2008;7: 125–37.CrossRefGoogle ScholarPubMed
38. Alves, S, Nascimento-Ferreira, I, Auregan, G, Hassig, R, Dufour, N, Brouillet, E, et al. Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease. PLoS ONE. 2008;3:e3341.CrossRefGoogle Scholar
39. Timmann, D, Gerwig, M, Frings, M, Maschke, M, Kolb, FP. Eyeblink conditioning in patients with hereditary ataxia: a one-year follow-up study. Exp Brain Res. 2005;162:332–45.CrossRefGoogle ScholarPubMed
40. França, MC Jr, D’Abreu, A, Nucci, A, Lopes-Cendes, I. Muscle excitability abnormalities in Machado-Joseph disease. Arch Neurol. 2008;65:525–9.CrossRefGoogle ScholarPubMed
41. Carvalho, DR, La Rocque-Ferreira, A, Rizzo, IM, Imamura, EU, Speck-Martins, CE. Homozygosity enhances severity in spinocerebellar ataxia type 3. Pediatr Neurol. 2008;38:296–9.CrossRefGoogle ScholarPubMed
42. Hellenbroich, Y, Gierga, K, Reusche, E, Schwinger, E, Deller, T, de Vos, RA, et al. Spinocerebellar ataxia type 4 (SCA4): initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration. J Neural Transm. 2006;113:829–43.CrossRefGoogle ScholarPubMed
43. Bour, LJ, van Rootselaar, AF, Koelman, JH, Tijssen, MA. Oculomotor abnormalities in myoclonic tremor: a comparison with spinocerebellar ataxia type 6. Brain. 2008;131:2295–303.CrossRefGoogle ScholarPubMed
44. Teive, HA, Munhoz, RP, Raskin, S, Werneck, LC. Spinocerebellar ataxia type 6 in Brazil. Arq Neuropsiquiatr. 2008;66:691–4.CrossRefGoogle ScholarPubMed
45. Christova, P, Anderson, JH, Gomez, CM. Impaired eye movements in presymptomatic spinocerebellar ataxia type 6. Arch Neurol. 2008;65:530–6.CrossRefGoogle ScholarPubMed
46. Kawai, Y, Suenaga, M, Watanabe, H, Ito, M, Kato, K, Kato, T, et al. Prefrontal hypoperfusion and cognitive dysfunction correlates in spinocerebellar ataxia type 6. J Neurol Sci. 2008;271:68–74.CrossRefGoogle ScholarPubMed
47. Kordasiewicz, HB, Gomez, CM. Molecular pathogenesis of spinocerebellar ataxia type 6. Neurotherapeutics. 2007;4:285–94.CrossRefGoogle ScholarPubMed
48. Garden, GA, La Spada, AR. Molecular pathogenesis and cellular pathology of spinocerebellar ataxia type 7 neurodegeneration. Cerebellum. 2008;7:138–49.CrossRefGoogle ScholarPubMed
49. Lin, Y, Zheng, JY, Jin, YH, Xie, YC, Jin, ZB. Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar ataxia and craniocervical dystonia. Neurosci Lett. 2008;434:230–3.CrossRefGoogle Scholar
50. Linhares Sda, C, Horta, WG, Cunha, FM, Castro, JD, Santos, AC, Marques, W Jr. Spastic paraparesis as the onset manifestation of spinocerebellar ataxia type 7. Arq Neuropsiquiatr. 2008;66: 246–8.CrossRefGoogle ScholarPubMed
51. Rüb, U, Brunt, ER, Seidel, K, Gierga, K, Mooy, CM, Kettner, M, et al. Spinocerebellar ataxia type 7 (SCA7): widespread brain damage in an adult-onset patient with progressive visual impairments in comparison with an adult-onset patient without visual impairments. Neuropathol Appl Neurobiol. 2008;34:155–68.CrossRefGoogle Scholar
52. Gupta, SN, Marks, HG. Spinocerebellar ataxia type 7 mimicking Kearns-Sayre syndrome: a clinical diagnosis is desirable. J Neurol Sci. 2008;264:173–6.CrossRefGoogle ScholarPubMed
53. Lilja, A, Hämäläinen, P, Kaitaranta, E, Rinne, R. Cognitive impairment in spinocerebellar ataxia type 8. J Neurol Sci. 2005;237:31–8.CrossRefGoogle ScholarPubMed
54. Wu, YR, Lin, HY, Chen, CM, Gwinn-Hardy, K, Ro, LS, Wang, YC, et al. Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson’s disease. Clin Genet. 2004;65:209–14.CrossRefGoogle ScholarPubMed
55. He, Y, Zu, T, Benzow, KA, Orr, HT, Clark, HB, Koob, MD. Targeted deletion of a single Sca8 ataxia locus allele in mice causes abnormal gait, progressive loss of motor coordination, and Purkinje cell dendritic deficits. J Neurosci. 2006;26:9975–82.CrossRefGoogle ScholarPubMed
56. Kumar, N, Miller, GM. White matter hyperintense lesions in genetically proven spinocerebellar ataxia 8. Clin Neurol Neurosurg. 2008;110:65–8.CrossRefGoogle ScholarPubMed
57. Munhoz, RP, Teive, HA, Raskin, S, Werneck, LC. CTA/CTG expansions at the SCA 8 locus in multiple system atrophy. Clin Neurol Neurosurg. 2009;111:208–10.CrossRefGoogle ScholarPubMed
58. Ohnari, K, Aoki, M, Uozumi, T, Tsuji, S. Severe symptoms of 16q-ADCA coexisting with SCA8 repeat expansion. J Neurol Sci. 2008;273:15–8.CrossRefGoogle ScholarPubMed
59. Torrens, L, Burns, E, Stone, J, Graham, C, Wright, H, Summers, D, et al. Spinocerebellar ataxia type 8 in Scotland: frequency, neurological, neuropsychological and neuropsychiatric findings. Acta Neurol Scand. 2008;11741–8.Google ScholarPubMed
60. Ito, H, Kawakami, H, Wate, R, Matsumoto, S, Imai, T, Hirano, A, et al. Clinicopathologic investigation of a family with expanded SCA8 CTA/CTG repeats. Neurology. 2006;67:1479–81.CrossRefGoogle ScholarPubMed
61. Mutsuddi, M, Rebay, I. Molecular genetics of spinocerebellar ataxia type 8 (SCA8). RNA Biol. 2005;2:49–52.CrossRefGoogle ScholarPubMed
62. Silveira, I, Alonso, I, Guimarães, L, Mendonča, P, Santos, C, Maciel, P, et al. High germinal instability of the (CTG)n at the SCA8 locus of both expanded and normal alleles. Am J Hum Genet. 2000;66:830–40.CrossRefGoogle ScholarPubMed
63. Chen, WL, Lin, JW, Huang, HJ, Wang, SM, Su, MT, Lee-Chen, GJ, et al. SCA8 mRNA expression suggests an antisense regulation of KLHL1 and correlates to SCA8 pathology. Brain Res. 2008;1233:176–84.CrossRefGoogle ScholarPubMed
64. Ikeda, Y, Daughters, RS, Ranum, LP. Bidirectional expression of the SCA8 expansion mutation: One mutation, two genes. Cerebellum. 2008;7:150–8.CrossRefGoogle ScholarPubMed
65. Moseley, ML, Zu, T, Ikeda, Y, Gao, W, Mosemiller, AK, Daughters, RS, et al. Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8. Nat Genet. 2006;38:758–69.CrossRefGoogle ScholarPubMed
66. Raskin, S, Ashizawa, T, Teive, HA, Arruda, WO, Fang, P, Gao, R, et al. Reduced penetrance in a Brazilian family with spinocerebellar ataxia type 10. Arch Neurol. 2007;64:591–4.CrossRefGoogle Scholar
67. Teive, HA, Arruda, WO, Raskin, S, Ashizawa, T, Werneck, LC. The history of spinocerebellar ataxia type 10 in Brazil: travels of a gene. Arq Neuropsiquiatr. 2007;65:965–8.CrossRefGoogle ScholarPubMed
68. Lin, X, Ashizawa, T. Recent progress in spinocerebellar ataxia type-10 (SCA10). Cerebellum. 2005;4:37–42.CrossRefGoogle ScholarPubMed
69. Rasmussen, A, Matsuura, T, Ruano, L, Yescas, P, Ochoa, A, Ashizawa, T, et al. Clinical and genetic analysis of four Mexican families with spinocerebellar ataxia type 10. Ann Neurol. 2001;50:234–9.CrossRefGoogle ScholarPubMed
70. Matsuura, T, Yamagata, T, Burgess, DL, Rasmussen, A, Grewal, RP, Watase, K et al. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet. 2000;26:191–4.CrossRefGoogle ScholarPubMed
71. Potaman, VN, Bissler, JJ, Hashem, VI, Oussatcheva, EA, Lu, L Shlyakhtenko, LS, et al. Unpaired structures in SCA10 (ATTCT)n.(AGAAT)n repeats. J Mol Biol. 2003;326:1095–111.CrossRefGoogle ScholarPubMed
72. Liu, G, Bissler, JJ, Sinden, RR, Leffak, M. Unstable spinocerebellar ataxia type 10 (ATTCT*(AGAAT) repeats are associated with aberrant replication at the ATX10 locus and replication origin-dependent expansion at an ectopic site in human cells. Mol Cell Biol. 2007;27:7828–38.CrossRefGoogle ScholarPubMed
73. März, P, Probst, A, Lang, S, Schwager, M, Rose-John, S, Otten, U, et al. Ataxin-10, the spinocerebellar ataxia type 10 neurodegenerative disorder protein, is essential for survival of cerebellar neurons. J Biol Chem. 2004;279:35542–50.CrossRefGoogle ScholarPubMed
74. Matsuura, T, Fang, P, Pearson, CE, Jayakar, P, Ashizawa, T, Roa, BB, et al. Interruptions in the expanded ATTCT repeat of spinocerebellar ataxia type 10: repeat purity as a disease modifier? Am J Hum Genet;2006;78:125–9.CrossRefGoogle ScholarPubMed
75. Matsuura, T, Fang, P, Lin, X, Khajavi, M, Tsuji, K, Rasmussen, A, et al. Somatic and germline instability of the ATTCT repeat in spinocerebellar ataxia type 10. Am J Hum Genet. 2004;74: 1216–24.CrossRefGoogle ScholarPubMed
76. Houlden, H, Johnson, J, Gardner-Thorpe, C, Lashley, T, Hernandez, D, Worth, P, et al. Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11. Nat Genet. 2007;39:1434–6.CrossRefGoogle ScholarPubMed
77. Bahl, S, Virdi, K, Mittal, U, Sachdeva, MP, Kalla, AK, Holmes, SE, et al. Evidence of a common founder for SCA12 in the Indian population. Ann Hum Genet. 2005;69:528–34.CrossRefGoogle ScholarPubMed
78. Dagda, RK, Merrill, RA, Cribbs, JT, Chen, Y, Hell, JW, Usachev, YM, et al. The spinocerebellar ataxia 12 gene product and protein phosphatase 2A regulatory subunit B(beta)2 antagonizes neuronal survival by promoting mitochondrial fission. J Biol Chem. 2008;283:36241–8.CrossRefGoogle Scholar
79. Stevanin, G, Durr, A, Benammar, N, Brice, A. Spinocerebellar ataxia with mental retardation (SCA13). Cerebellum. 2005;4:43–6.CrossRefGoogle ScholarPubMed
80. Miura, S, Nakagawara, H, Kaida, H, Sugita, M, Noda, K, Motomura, K, et al. Expansion of the phenotypic spectrum of SCA14 caused by the Gly128Asp mutation in PRKCG. Clin Neurol Neurosurg. 2009;111:211–5.CrossRefGoogle ScholarPubMed
81. Klebe, S, Durr, A, Rentschler, A, Hahn-Barma, V, Abele, M, Bouslam, N, et al. New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14. Ann Neurol. 2005;58:720–9.CrossRefGoogle ScholarPubMed
82. Morita, H, Yoshida, K, Suzuki, K, Ikeda, S. A Japanese case of SCA14 with the Gly128Asp mutation. J Hum Genet. 2006;51:1118–21.CrossRefGoogle ScholarPubMed
83. Seki, T, Shimahara, T, Yamamoto, K, Abe, N, Amano, T, Adachi, N, et al. Mutant gammaPKC found in spinocerebellar ataxia type 14 induces aggregate-independent maldevelopment of dendrites in primary cultured Purkinje cells. Neurobiol Dis. 2009;33:260–73.CrossRefGoogle ScholarPubMed
84. Verbeek, DS, Goedhart, J, Bruinsma, L, Sinke, RJ, Reits, EA. PKC gamma mutations in spinocerebellar ataxia type 14 affect C1 domain accessibility and kinase activity leading to aberrant MAPK signaling. J Cell Sci. 2008;121:2339–49.CrossRefGoogle ScholarPubMed
85. Adachi, N, Kobayashi, T, Takahashi, H, Kawasaki, T, Shirai, Y, Ueyama, T, et al. Enzymological analysis of mutant protein kinase Cgamma causing spinocerebellar ataxia type 14 and dysfunction in Ca2+ homeostasis. J Biol Chem. 2008;283: 19854–63.CrossRefGoogle ScholarPubMed
86. Knight, MA, Kennerson, ML, Anney, RJ, Matsuura, T, Nicholson, GA, Salimi-Tari, P, et al. Spinocerebellar ataxia type 15 (sca15) maps to 3p24.2-3pter: exclusion of the ITPR1 gene, the human orthologue of an ataxic mouse mutant. Neurobiol Dis. 2003;13:147–57.CrossRefGoogle ScholarPubMed
87. Gardner, RJ, Knight, MA, Hara, K, Tsuji, S, Forrest, SM, Storey, E. Spinocerebellar ataxia type 15. Cerebellum. 2005;4:47–50.CrossRefGoogle ScholarPubMed
88. Miyoshi, Y, Yamada, T, Tanimura, M, Taniwaki, T, Arakawa, K, Ohyagi, Y, et al. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology. 2001;57:96–100.CrossRefGoogle ScholarPubMed
89. Hara, K, Shiga, A, Nozaki, H, Mitsui, J, Takahashi, Y, Ishiguro, H, et al. Total deletion and a missense mutation of ITPR1 in Japanese SCA15 families. Neurology. 2008;71:547–51.CrossRefGoogle Scholar
90. Iwaki, A, Kawano, Y, Miura, S, Shibata, H, Matsuse, D, Li, W, et al. Heterozygous deletion of ITPR1, but not SUMF1, in spinocerebellar ataxia type 16. J Med Genet. 2008;45:32–5.CrossRefGoogle Scholar
91. Gao, R, Matsuura, T, Coolbaugh, M, Zühlke, C, Nakamura, K, Rasmussen, A, et al. Instability of expanded CAG/CAA repeats in spinocerebellar ataxia type 17. Eur J Hum Genet. 2008;16: 215–22.CrossRefGoogle ScholarPubMed
92. Mariotti, C, Alpini, D, Fancellu, R, Soliveri, P, Grisoli, M, Ravaglia, S, et al. Spinocerebellar ataxia type 17 (SCA17): oculomotor phenotype and clinical characterization of 15 Italian patients. J Neurol. 2007;254:1538–46.CrossRefGoogle ScholarPubMed
93. Stevanin, G, Brice, A. Spinocerebellar ataxia 17 (SCA17) and Huntington’s disease-like 4 (HDL4). Cerebellum. 2008;7:170–8.CrossRefGoogle ScholarPubMed
94. Lasek, K, Lencer, R, Gaser, C, Hagenah, J, Walter, U, Wolters, A et al. Morphological basis for the spectrum of clinical deficits in spinocerebellar ataxia 17 (SCA17). Brain. 2006;129:2341–52.CrossRefGoogle ScholarPubMed
95. Lee, LC, Chen, CM, Chen, FL, Lin, PY, Hsiao, YC, Wang, Pr, et al. Altered expression of HSPA5, HSPA8 and PARK7 in spinocerebellar ataxia type 17 identified by 2-dimensional fluorescence difference in gel electrophoresis. Clin Chim Acta. 2009;400:56–62.CrossRefGoogle ScholarPubMed
96. Schelhaas, HJ, van de Warrenburg, BP. Clinical, psychological, and genetic characteristics of spinocerebellar ataxia type 19 (SCA19). Cerebellum. 2005;4:51–4.CrossRefGoogle Scholar
97. Verbeek, DS, Schelhaas, JH, Ippel, EF, Beemer, FA, Pearson, PL, Sinke, RJ. Identification of a novel SCA locus (SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet. 2002;111:388–93.CrossRefGoogle Scholar
98. Knight, MA, Hernandez, D, Diede, SJ, Dauwerse, HG, Rafferty, I, van de Leemput, J, et al. A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20. Hum Mol Genet. 2008;17:3847–53.CrossRefGoogle ScholarPubMed
99. Storey, E, Knight, MA, Forrest, SM, Gardner, RJ. Spinocerebellar ataxia type 20. Cerebellum. 2005;4:55–7.CrossRefGoogle ScholarPubMed
100. Delplanque, J, Devos, D, Vuillaume, I, De Becdelievre, A, Vangelder, E, Maurage, CA, et al. Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). Cerebellum. 2008;7:179–83.CrossRefGoogle ScholarPubMed
101. Knight, MA, Gardner, RJ, Bahlo, M, Matsuura, T, Dixon, JA, Forrest, SM, et al. Dominantly inherited ataxia and dysphonia with dentate calcification: spinocerebellar ataxia type 20. Brain. 2004;127:1172–81.CrossRefGoogle ScholarPubMed
102. Vuillaume, I, Devos, D, Schraen-Maschke, S, Dina, C, Lemainque, A, Vasseur, F, et al. A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. Ann Neurol. 2002;52: 666–70.CrossRefGoogle ScholarPubMed
103. Chung, MY, Lu, YC, Cheng, NC, Soong, BW. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain. 2003;126:1293–9.CrossRefGoogle ScholarPubMed
104. Verbeek, DS, van de Warrenburg, BP, Wesseling, P, Pearson, PL, Kremer, HP, Sinke, RJ. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain. 2004;127:2551–7.CrossRefGoogle Scholar
105. Yu, GY, Howell, MJ, Roller, MJ, Xie, TD, Gomez, CM. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol. 2005;57:349–54.CrossRefGoogle ScholarPubMed
106. Brusse, E, de Koning, I, Maat-Kievit, A, Oostra, BA, Heutink, P, van Swieten, JC. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype. Mov Disord. 2006;21:396–401.CrossRefGoogle ScholarPubMed
107. Mariotti, C, Brusco, A, Di Bella, D, Cagnoli, C, Seri, M, Gellera, C, et al. Spinocerebellar ataxia type 28: A novel autosomal dominant cerebellar ataxia characterized by slow progression and ophthalmoparesis. Cerebellum. 2008;7:184–8.CrossRefGoogle ScholarPubMed
108. Cagnoli, C, Mariotti, C, Taroni, F, Seri, M, Brussino, A, Michielotto, C, et al. SCA28, a novel form of autosomal dominant cerebellar ataxia on chromosome 18p11.22-q11.2. Brain. 2006;129:235–42 CrossRefGoogle ScholarPubMed
109. Oyanagi, S. Hereditary dentatorubral-pallidoluysian atrophy. Neuropathology. 2000;20 suppl:S42–6.CrossRefGoogle ScholarPubMed
110. Garcia Ruiz, PJ, Mayo, D, Hernandez, J, Cantarero, S, Ayuso, C. Movement disorders in hereditary ataxias. J Neurol Sci. 2002;202;59–64.CrossRefGoogle ScholarPubMed
111. Jen, JC. Hereditary episodic ataxias. Ann N Y Acad Sci. 2008;1142: 250–3.CrossRefGoogle ScholarPubMed
112. Klockgether, T. Recent advances in degenerative ataxias. Curr Opin Neurol. 2000;13:451–5.CrossRefGoogle ScholarPubMed
113. Riant, F, Mourtada, R, Saugier-Veber, P, Tournier-Lasserve, E. Large CACNA1A deletion in a family with episodic ataxia type 2. Arch Neurol. 2008;65:817–20.CrossRefGoogle Scholar
114. Steckley, JL, Ebers, GC, Cader, MZ, McLachlan, RS. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology. 2001;57:1499–502.CrossRefGoogle ScholarPubMed
115. Cader, MZ, Steckley, JL, Dyment, DA, McLachlan, RS, Ebers, GC. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. 2005;65:156–8.CrossRefGoogle ScholarPubMed
116. Damji, KF, Allingham, RR, Pollock, SC, Small, K, Lewis, KE, Stajich, JM, et al. Periodic vestibulocerebellar ataxia, an autosomal dominant ataxia with defective smooth pursuit, is genetically distinct from other autosomal dominant ataxias. Arch Neurol. 1996;53:338–44.CrossRefGoogle ScholarPubMed
117. Escayg, A, De Waard, M, Lee, DD, Bichet, D, Wolf, P, Mayer, T, et al. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000;66:1531–9.CrossRefGoogle ScholarPubMed
118. Kerber, KA, Jen, JC, Lee, H, Nelson, SF, Baloh, RW. A new episodic ataxia syndrome with linkage to chromosome 19q13. Arch Neurol. 2007;64:749–52.CrossRefGoogle ScholarPubMed
119. Debray, FG, Lambert, M, Gagne, R, Maranda, B, Laframboise, R, MacKay, N, et al. Pyruvate dehydrogenase deficiency presenting as intermittent isolated acute ataxia. Neuropediatrics. 2008;39: 20–3.CrossRefGoogle ScholarPubMed
120. Craig, K, Elliott, HR, Keers, SM, Lambert, C, Pyle, A, Graves, TD, et al. Episodic ataxia and hemiplegia caused by the 8993T>C mitochondrial DNA mutation. J Med Genet. 2007;44:797–9.CrossRefGoogle ScholarPubMed
121. Finsterer, J. Mitochondrial ataxias. Eur J Neurol. In Press 2009.CrossRefGoogle Scholar
122. Finsterer, J. Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol. 2008;39:223–35 CrossRefGoogle ScholarPubMed
123. Di Donato, S, Gellera, C, Mariotti, C. The complex clinical and genetic classification of inherited ataxias. II. Autosomal recessive ataxias. Neurol Sci. 2001;22:219–28.CrossRefGoogle ScholarPubMed
124. Koeppen, AH, Michael, SC, Knutson, MD, Haile, DJ, Qian, J, Levi, S, et al. The dentate nucleus in Friedreich’s ataxia: the role of ironresponsive proteins. Acta Neuropathol. 2007;114:163–73.CrossRefGoogle ScholarPubMed
125. Hirai, T, Suzuki, M, Kurita, A, Inoue, K. Neurological findings, neurophysiological examinations, and sural nerve biopsy in a case of Friedreich ataxia. Rinsho Shinkeigaku. 2006;46:485–90.Google Scholar
126. Fayssoil, A, Nardi, O, Orlikowski, D, Annane, D. Hypertrophic cardiomyopathy in Friedreich’s ataxia. Int J Cardiol. 2008;127:e122–3.CrossRefGoogle ScholarPubMed
127. Whitnall, M, Rahmanto, YS, Sutak, R, Xu, X, Becker, EM, Mikhael, MR, et al. The MCK mouse heart model of Friedreich’s ataxia: Alterations in iron-regulated proteins and cardiac hypertrophy are limited by iron chelation. Proc Natl Acad Sci USA. 2008;105:9757–62.CrossRefGoogle ScholarPubMed
128. Raman, SV, Dickerson, JA, Al-Dahhak, R. Myocardial ischemia in the absence of epicardial coronary artery disease in Friedreich’s ataxia. J Cardiovasc Magn Reson. 2008;10:15.CrossRefGoogle ScholarPubMed
129. Milbrandt, TA, Kunes, JR, Karol, LA. Friedreich’s ataxia and scoliosis: the experience at two institutions. J Pediatr Orthop. 2008;28:234–8.CrossRefGoogle ScholarPubMed
130. Galimanis, A, Glutz, L, Spiegel, R, Burgunder, JM, Kaelin-Lang, A. Very-late-onset Friedreich ataxia with disturbing head tremor and without spinal atrophy-a case report. Mov Disord. 2008;23:1058–9.CrossRefGoogle ScholarPubMed
131. Ribaï, P, Pousset, F, Tanguy, ML, Rivaud-Pechoux, S, Le Ber, I, Gasparini, F, et al. Neurological, cardiological, and oculomotor progression in 104 patients with Friedreich ataxia during long-term follow-up. Arch Neurol. 2007;64:558–64.CrossRefGoogle ScholarPubMed
132. Della Nave, R, Ginestroni, A, Tessa, C, Salvatore, E, Bartolomei, I, Salvi, F, et al. Brain white matter tracts degeneration in Friedreich ataxia. An in vivo MRI study using tract-based spatial statistics and voxel-based morphometry. Neuroimage. 2008;40:19–25.CrossRefGoogle Scholar
133. Popescu, BF, Pickering, IJ, George, GN, Nichol, H. The chemical form of mitochondrial iron in Friedreich’s ataxia. J Inorg Biochem. 2007;101:957–66.CrossRefGoogle ScholarPubMed
134. Pandolfo, M. Friedreich ataxia: Detection of GAA repeat expansions and frataxin point mutations. Methods Mol Med. 2006;126: 197–216.Google ScholarPubMed
135. Wells, RD. DNA triplexes and Friedreich ataxia. FASEB J. 2008;22:1625–34.CrossRefGoogle ScholarPubMed
136. Hebert, MD. Targeting the gene in Friedreich ataxia. Biochimie. 2008;90:1131–9.CrossRefGoogle ScholarPubMed
137. Greene, E, Mahishi, L, Entezam, A, Kumari, D, Usdin, K. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res. 2007;35:3383–90.CrossRefGoogle ScholarPubMed
138. Gellera, C, Castellotti, B, Mariotti, C, Mineri, R, Seveso, V, Didonato, S, et al. Frataxin gene point mutations in Italian Friedreich ataxia patients. Neurogenetics. 2007;8:289–99.CrossRefGoogle ScholarPubMed
139. Reddy, PL, Grewal, RP. Friedreich’s ataxia: a clinical and genetic analysis. Clin Neurol Neurosurg. 2007;109:200–2.CrossRefGoogle ScholarPubMed
140. De Biase, I, Rasmussen, A, Monticelli, A, Al-Mahdawi, S, Pook, M, Cocozza, S, et al. Somatic instability of the expanded GAA triplet-repeat sequence in Friedreich ataxia progresses throughout life. Genomics. 2007;90:1–5.CrossRefGoogle ScholarPubMed
141. Federico, A. Ataxia with isolated vitamin E deficiency: a treatable neurologic disorder resembling Friedreich’s ataxia. Neurol Sci. 2004;25:119–21.CrossRefGoogle ScholarPubMed
142. Marzouki, N, Benomar, A, Yahyaoui, M, Birouk, N, Elouazzani, M, Chkili, T, et al. Vitamin E deficiency ataxia with (744 del A) mutation on alpha-TTP gene: genetic and clinical peculiarities in Moroccan patients. Eur J Med Genet. 2005;48:21–8.CrossRefGoogle Scholar
143. Gabsi, S, Gouider-Khouja, N, Belal, S, Fki, M, Kefi, M, Turki, I, et al. Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. Eur J Neurol. 2001;8:477–81.CrossRefGoogle ScholarPubMed
144. Finsterer, J, Regelsberger, G, Voigtländer, T. Refsum disease due to the splice-site mutation c.135-2A>G before exon 3 of the PHYH gene, diagnosed eight years after detection of retinitis pigmentosa. J Neurol Sci. 2008;266:182–186.CrossRefGoogle Scholar
145. Staples, ER, McDermott, EM, Reiman, A, Byrd, PJ, Ritchie, S, Taylor, AM, et al. Immunodeficiency in ataxia telangiectasia is correlated strongly with the presence of two null mutations in the ataxia telangiectasia mutated gene. Clin Exp Immunol. 2008;153:214–20.CrossRefGoogle ScholarPubMed
146. Biton, S, Barzilai, A, Shiloh, Y. The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle. DNA Repair (Amst). 2008;7:1028–38.CrossRefGoogle ScholarPubMed
147. Habek, M, Brinar, VV, Rados, M, Zadro, I, Zarković, K. Brain MRI abnormalities in ataxia-telangiectasia. Neurologist. 2008;14: 192–5.CrossRefGoogle ScholarPubMed
148. Taylor, AM, Byrd, PJ. Molecular pathology of ataxia telangiectasia. J Clin Pathol. 2005;58:1009–15.CrossRefGoogle ScholarPubMed
149. Le, B, I, Brice, A, Durr, A. New autosomal recessive cerebellar ataxias with oculomotor apraxia. Curr Neurol Neurosci Rep. 2005;5:411–7.Google Scholar
150. Engert, JC, Bérubé, P, Mercier, J, Doré, C, Lepage, P, Ge, B, et al. ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF. Nat Genet. 2000;24:120–5.CrossRefGoogle Scholar
151. Senderek, J, Krieger, M, Stendel, C, Bergmann, C, Moser, M, Breitbach-Faller, N, et al. Mutations in SIL1 cause Marinesco-Sjögren syndrome, a cerebellar ataxia with cataract and myopathy. Nat Genet. 2005;37:1312–4.CrossRefGoogle ScholarPubMed
152. Adams, SA, Steenblock, KJ, Thibodeau, SN, Lindor, NM. Premutations in the FMR1 gene are uncommon in men undergoing genetic testing for spinocerebellar ataxia. J Neurogenet. 2008;22:77–92.CrossRefGoogle ScholarPubMed
153. Berry-Kravis, E, Abrams, L, Coffey, SM, Hall, DA, Greco, C, Gane, LW, et al. Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines. Mov Disord. 2007;22:2018–30.CrossRefGoogle ScholarPubMed
154. Mascalchi, M. Spinocerebellar ataxias. Neurol Sci. 2008;29 suppl 3:311–3.CrossRefGoogle ScholarPubMed
155. Allikmets, R, Raskind, WH, Hutchinson, A, Schueck, ND, Dean, M, Koeller, DM. Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum Mol Genet. 1999;8:743–9.CrossRefGoogle ScholarPubMed
156. Hellier, KD, Hatchwell, E, Duncombe, AS, Kew, J, Hammans, SR. X-linked sideroblastic anaemia with ataxia: another mitochondrial disease? J Neurol Neurosurg Psychiatry. 2001;70:65–9.CrossRefGoogle ScholarPubMed
157. Maguire, A, Hellier, K, Hammans, S, May, A. X-linked cerebellar ataxia and sideroblastic anaemia associated with a missense mutation in the ABC7 gene predicting V411L. Br J Haematol. 2001;115:910–7.CrossRefGoogle ScholarPubMed
158. Schmitz-Hübsch, T, Klockgether, T. An update on inherited ataxias. Curr Neurol Neurosci Rep. 2008;8:310–9.CrossRefGoogle ScholarPubMed
159. Schöls, L, Arning, L, Schüle, R, Epplen, JT, Timmann, D. “Pseudodominant inheritance” of ataxia with ocular apraxia type 2 (AOA2). J Neurol. 2008;255:495–501.CrossRefGoogle ScholarPubMed
160. Ogawa, M. Pharmacological treatments of cerebellar ataxia. Cerebellum. 2004;3:107–11.CrossRefGoogle ScholarPubMed
161. Di Prospero, NA, Baker, A, Jeffries, N, Fischbeck, KH. Neurological effects of high-dose idebenone in patients with Friedreich’s ataxia: a randomised, placebo-controlled trial. Lancet Neurol. 2007;6:878–86.CrossRefGoogle ScholarPubMed
162. Boesch, S, Sturm, B, Hering, S, Goldenberg, H, Poewe, W, Scheiber-Mojdehkar, B. Friedreich’s ataxia: clinical pilot trial with recombinant human erythropoietin. Ann Neurol. 2007;62:521–4.CrossRefGoogle ScholarPubMed
163. Boddaert, N, Le Quan Sang, KH, Rötig, A, Leroy-Willig, A, Gallet, S, Brunelle, F, et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood. 2007;110:401–8.CrossRefGoogle ScholarPubMed
164. Goulipian, C, Bensoussan, L, Viton, JM, Milhe-De Bovis, V, Ramon, J, Delarque, A. Orthopedic shoes improve gait in Friedreich’s ataxia: a clinical and quantified case study. Eur J Phys Rehabil Med. 2008;44:93–8.Google ScholarPubMed
165. Gazulla, J, Modrego, P. Buspirone and serotonin in spinocerebellar ataxia. J Neurol Sci. 2008;268:199–200.CrossRefGoogle ScholarPubMed
166. Underwood, BR, Rubinsztein, DC. Spinocerebellar ataxias caused by polyglutamine expansions: a review of therapeutic strategies. Cerebellum. 2008;7:215–21.CrossRefGoogle ScholarPubMed