spinocerebellar ataxias

Summary

Summary: A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)

Top Publications

  1. Miyatake S, Miyake N, Doi H, Saitsu H, Ogata K, Kawai M, et al. A novel SACS mutation in an atypical case with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Intern Med. 2012;51:2221-6 pubmed
    ..We should be aware of atypical features of ARSACS for the correct diagnosis...
  2. Forman O, De Risio L, Stewart J, Mellersh C, Beltran E. Genome-wide mRNA sequencing of a single canine cerebellar cortical degeneration case leads to the identification of a disease associated SPTBN2 mutation. BMC Genet. 2012;13:55 pubmed publisher
    ..We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation...
  3. Fryer J, Yu P, Kang H, Mandel Brehm C, Carter A, Crespo Barreto J, et al. Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science. 2011;334:690-3 pubmed publisher
    ..Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases...
  4. Barnes J, Ebner B, Duvick L, Gao W, Chen G, Orr H, et al. Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice. J Neurosci. 2011;31:12778-89 pubmed publisher
    ..For polyglutamine diseases generally, the findings support a model whereby specific neuronal circuits suffer insults that alter function before cell death...
  5. Stankewich M, Gwynn B, Ardito T, Ji L, Kim J, Robledo R, et al. Targeted deletion of betaIII spectrin impairs synaptogenesis and generates ataxic and seizure phenotypes. Proc Natl Acad Sci U S A. 2010;107:6022-7 pubmed publisher
    ..The mislocalization of these proteins secondarily disrupts glutamate transport dynamics, leading to seizures, neuronal damage, and compensatory changes in EAAT3 and neuropeptide Y...
  6. Schmitz Hubsch T, Coudert M, Tezenas du Montcel S, Giunti P, Labrum R, Durr A, et al. Depression comorbidity in spinocerebellar ataxia. Mov Disord. 2011;26:870-6 pubmed publisher
    ..Despite a higher risk for depression with more severe disease, the relation of depressive symptoms to SCA neurodegeneration remains to be shown...
  7. Nelson D, Orr H, Warren S. The unstable repeats--three evolving faces of neurological disease. Neuron. 2013;77:825-43 pubmed publisher
    ..In addition to providing insight into the mechanisms underlying these devastating neurological disorders, the study of these unstable microsatellite repeat disorders has provided insight into very basic aspects of neuroscience...
  8. Sailer A, Scholz S, Gibbs J, Tucci A, Johnson J, Wood N, et al. Exome sequencing in an SCA14 family demonstrates its utility in diagnosing heterogeneous diseases. Neurology. 2012;79:127-31 pubmed publisher
    ..Here we describe the use of exome sequencing to investigate a large, 5-generational British kindred with an autosomal dominant, progressive cerebellar ataxia in which conventional genetic testing had not revealed a causal etiology...
  9. Orr H. Cell biology of spinocerebellar ataxia. J Cell Biol. 2012;197:167-77 pubmed publisher
    ..Thus, understanding the cellular function of these proteins could aid in the development of therapeutics...

More Information

Publications62

  1. Gazulla J, Benavente I, Vela A, Marin M, Pablo L, Tessa A, et al. New findings in the ataxia of Charlevoix-Saguenay. J Neurol. 2012;259:869-78 pubmed publisher
    ..The distinctive aspect of the dorsal spine could be of help in the clinical diagnosis...
  2. Ingram M, Orr H, Clark H. Genetically engineered mouse models of the trinucleotide-repeat spinocerebellar ataxias. Brain Res Bull. 2012;88:33-42 pubmed publisher
    The spinocerebellar ataxias (SCAs) are dominantly inherited disorders that primarily affect coordination of motor function but also frequently involve other brain functions...
  3. Gazulla J, Vela A, Marin M, Pablo L, Santorelli F, Benavente I, et al. Is the ataxia of Charlevoix-Saguenay a developmental disease?. Med Hypotheses. 2011;77:347-52 pubmed publisher
    ..These observations should be taken into account when research about the origin of ARSACS is undertaken...
  4. GEHRKING K, Andresen J, Duvick L, Lough J, Zoghbi H, Orr H. Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet. 2011;20:2204-12 pubmed publisher
    ..We also showed that genetic background modulated ATXN1[82Q]-induced phenotypes. Of interest, these latter studies showed that some phenotypes are enhanced on a mixed background while others are suppressed...
  5. Tzoulis C, Neckelmann G, Mørk S, Engelsen B, Viscomi C, Moen G, et al. Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes. Brain. 2010;133:1428-37 pubmed publisher
    ..We suggest therefore that both infantile and later onset polymerase gamma related encephalopathies are part of a continuum...
  6. Di Gregorio E, Orsi L, Godani M, Vaula G, Jensen S, Salmon E, et al. Two Italian families with ITPR1 gene deletion presenting a broader phenotype of SCA15. Cerebellum. 2010;9:115-23 pubmed publisher
  7. Ishiguro T, Ishikawa K, Takahashi M, Obayashi M, Amino T, Sato N, et al. The carboxy-terminal fragment of alpha(1A) calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells. Acta Neuropathol. 2010;119:447-64 pubmed publisher
    ..1 with Q28 did. We conclude that SCA6 pathogenesis may be associated with the CTF, normally found in the cytoplasm, being aggregated in the cytoplasm and additionally distributed in the nucleus...
  8. Teive H. Spinocerebellar ataxias. Arq Neuropsiquiatr. 2009;67:1133-42 pubmed
    b>Spinocerebellar ataxias (SCAs) constitute a heterogeneous group of neurodegenerative diseases characterized by progressive cerebellar ataxia in association with some or all of the following conditions: ophthalmoplegia, pyramidal signs, ..
  9. Bauer P, Stevanin G, Beetz C, Synofzik M, Schmitz Hubsch T, Wullner U, et al. Spinocerebellar ataxia type 11 (SCA11) is an uncommon cause of dominant ataxia among French and German kindreds. J Neurol Neurosurg Psychiatry. 2010;81:1229-32 pubmed publisher
  10. Pula J, Gomez C, Kattah J. Ophthalmologic features of the common spinocerebellar ataxias. Curr Opin Ophthalmol. 2010;21:447-53 pubmed publisher
    The spinocerebellar ataxias (SCAs) are a phenotypically and genetically diverse group of autosomal dominant disorders that cause pathological degeneration in the cerebellum, brainstem, and retina, resulting in a wide variety of ..
  11. Teive H, Munhoz R, Raskin S, Arruda W, De Paola L, Werneck L, et al. Spinocerebellar ataxia type 10: Frequency of epilepsy in a large sample of Brazilian patients. Mov Disord. 2010;25:2875-8 pubmed publisher
    ..Overall, the frequency of epilepsy was considered rare, been found in 3.75 % of the cases while this finding in populations from other geographic areas reaches 60% of SCA10 cases. ..
  12. OZ G, Iltis I, Hutter D, Thomas W, Bushara K, Gomez C. Distinct neurochemical profiles of spinocerebellar ataxias 1, 2, 6, and cerebellar multiple system atrophy. Cerebellum. 2011;10:208-17 pubmed publisher
    ..We compared cerebellar and brainstem neurochemical profiles measured at 4 T from 26 patients with spinocerebellar ataxias (SCA1, N?=?9; SCA2, N?=?7; SCA6, N?=?5) or cerebellar multiple system atrophy (MSA-C, N?=?5) and 15 age-..
  13. Sequeiros J, Seneca S, Martindale J. Consensus and controversies in best practices for molecular genetic testing of spinocerebellar ataxias. Eur J Hum Genet. 2010;18:1188-95 pubmed publisher
    Many laboratories worldwide are offering molecular genetic testing for spinocerebellar ataxias (SCAs). This is essential for differential diagnosis and adequate genetic counselling...
  14. Wang J, Yang X, Xia K, Hu Z, Weng L, Jin X, et al. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain. 2010;133:3510-8 pubmed publisher
    Autosomal-dominant spinocerebellar ataxias constitute a large, heterogeneous group of progressive neurodegenerative diseases with multiple types...
  15. Chintawar S, Hourez R, Ravella A, Gall D, Orduz D, Rai M, et al. Grafting neural precursor cells promotes functional recovery in an SCA1 mouse model. J Neurosci. 2009;29:13126-35 pubmed publisher
    ..We postulate that a similar neuroprotective effect of NPCs may be applicable to other cerebellar degenerative diseases...
  16. Kozlov G, Denisov A, Girard M, Dicaire M, Hamlin J, McPherson P, et al. Structural basis of defects in the sacsin HEPN domain responsible for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). J Biol Chem. 2011;286:20407-12 pubmed publisher
    ..This study provides novel insights into the oligomerization state of sacsin and functions that are lost in mutations that cause ARSACS...
  17. Solodkin A, Gomez C. Spinocerebellar ataxia type 6. Handb Clin Neurol. 2012;103:461-73 pubmed publisher
    The autosomal dominant spinocerebellar ataxias (SCA) are a genetically heterogeneous group of neurodegenerative disorders characterized by progressive motor incoordination, in some cases with ataxia alone and in others in association ..
  18. Yamazaki H, Nozaki H, Onodera O, Michikawa T, Nishizawa M, Mikoshiba K. Functional characterization of the P1059L mutation in the inositol 1,4,5-trisphosphate receptor type 1 identified in a Japanese SCA15 family. Biochem Biophys Res Commun. 2011;410:754-8 pubmed publisher
    ..These results demonstrate that the Ca(2+) release properties of IP(3)R1 are largely unaffected by the P1059L mutation...
  19. Nag N, Tarlac V, Storey E. Assessing the efficacy of specific cerebellomodulatory drugs for use as therapy for spinocerebellar ataxia type 1. Cerebellum. 2013;12:74-82 pubmed publisher
    b>Spinocerebellar ataxias are autosomal dominant diseases, associated in some types with a CAG repeat expansion, and characterised by a progressive loss of motor function...
  20. Seyhan A. RNAi: a potential new class of therapeutic for human genetic disease. Hum Genet. 2011;130:583-605 pubmed publisher
    ..In this review, progress and challenges in developing RNAi therapeutics for genetic diseases will be discussed...
  21. Foskett J. Inositol trisphosphate receptor Ca2+ release channels in neurological diseases. Pflugers Arch. 2010;460:481-94 pubmed publisher
    ..diseases caused by mutations in other genes, including Huntington's and Alzheimer's diseases and some spinocerebellar ataxias, where the mutant proteins have been found to exert strong influences on InsP3R function that may link ..
  22. Bezprozvanny I. Role of inositol 1,4,5-trisphosphate receptors in pathogenesis of Huntington's disease and spinocerebellar ataxias. Neurochem Res. 2011;36:1186-97 pubmed publisher
    Huntington's disease (HD) and spinocerebellar ataxias (SCAs) are autosomal-dominant neurodegenerative disorders...
  23. Furrer S, Mohanachandran M, Waldherr S, Chang C, Damian V, Sopher B, et al. Spinocerebellar ataxia type 7 cerebellar disease requires the coordinated action of mutant ataxin-7 in neurons and glia, and displays non-cell-autonomous bergmann glia degeneration. J Neurosci. 2011;31:16269-78 pubmed publisher
    ..These findings indicate that SCA7 disease pathogenesis involves a convergence of alterations in a variety of different cell types to fully recapitulate the cerebellar degeneration...
  24. Hadjivassiliou M, Wallis L, Hoggard N, Grunewald R, Griffiths P, Wilkinson I. MR spectroscopy and atrophy in Gluten, Friedreich's and SCA6 ataxias. Acta Neurol Scand. 2012;126:138-43 pubmed publisher
    ..Previous work using proton MR spectroscopy ((1)H-MRS) of the cerebellum in the ataxias suggested that (1)H-MRS abnormalities and atrophy do not necessarily occur concurrently...
  25. van Gaalen J, Giunti P, van de Warrenburg B. Movement disorders in spinocerebellar ataxias. Mov Disord. 2011;26:792-800 pubmed publisher
    Autosomal dominant spinocerebellar ataxias (SCAs) can present with a large variety of noncerebellar symptoms, including movement disorders...
  26. Jafar Nejad P, Ward C, Richman R, Orr H, Zoghbi H. Regional rescue of spinocerebellar ataxia type 1 phenotypes by 14-3-3epsilon haploinsufficiency in mice underscores complex pathogenicity in neurodegeneration. Proc Natl Acad Sci U S A. 2011;108:2142-7 pubmed publisher
    ..These data suggest that distinct pathogenic mechanisms operate in different vulnerable brain regions, adding another level of complexity to SCA1 pathogenesis...
  27. Nolte D, Sobanski E, Wissen A, Regula J, Lichy C, Muller U. Spinocerebellar ataxia type 17 associated with an expansion of 42 glutamine residues in TATA-box binding protein gene. J Neurol Neurosurg Psychiatry. 2010;81:1396-9 pubmed publisher
    ..Spinocerebellar ataxia type 17 (SCA17) is caused by abnormal expansions of CAG/CAA trinucleotides within the TATA-box binding protein gene (TBP). The currently accepted critical threshold of abnormal expansions is ?43...
  28. Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, et al. Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet. 2009;85:544-57 pubmed publisher
    ..Our finding suggests that the ectopic microsatellite repeat, when transcribed, might cause a disease involving the essential splicing factors...
  29. Schmitz Hubsch T, Fimmers R, Rakowicz M, Rola R, Zdzienicka E, Fancellu R, et al. Responsiveness of different rating instruments in spinocerebellar ataxia patients. Neurology. 2010;74:678-84 pubmed publisher
    ..To determine the longitudinal metric properties of recently developed clinical assessment tools in spinocerebellar ataxia (SCA)...
  30. Reetz K, Lencer R, Hagenah J, Gaser C, Tadic V, Walter U, et al. Structural changes associated with progression of motor deficits in spinocerebellar ataxia 17. Cerebellum. 2010;9:210-7 pubmed publisher
  31. Hallen L, Klein H, Stoschek C, Wehrmeyer S, Nonhoff U, Ralser M, et al. The KRAB-containing zinc-finger transcriptional regulator ZBRK1 activates SCA2 gene transcription through direct interaction with its gene product, ataxin-2. Hum Mol Genet. 2011;20:104-14 pubmed publisher
    ..Thus, our results provide first evidence that ataxin-2 acts as a co-regulator of ZBRK1 activating its own transcription, thereby representing the first identified ZBRK1 co-activator...
  32. Clarkson Y, Gillespie T, Perkins E, Lyndon A, Jackson M. Beta-III spectrin mutation L253P associated with spinocerebellar ataxia type 5 interferes with binding to Arp1 and protein trafficking from the Golgi. Hum Mol Genet. 2010;19:3634-41 pubmed publisher
  33. Teive H, Munhoz R, Arruda W, Lopes Cendes I, Raskin S, Werneck L, et al. Spinocerebellar ataxias: genotype-phenotype correlations in 104 Brazilian families. Clinics (Sao Paulo). 2012;67:443-9 pubmed
    b>Spinocerebellar ataxias are neurodegenerative disorders involving the cerebellum and its connections. There are more than 30 distinct subtypes, 16 of which are associated with an identified gene...
  34. Anesi L, de Gemmis P, Pandolfo M, Hladnik U. Two novel homozygous SACS mutations in unrelated patients including the first reported case of paternal UPD as an etiologic cause of ARSACS. J Mol Neurosci. 2011;43:346-9 pubmed publisher
  35. Brusse E, Brusse Keizer M, Duivenvoorden H, van Swieten J. Fatigue in spinocerebellar ataxia: patient self-assessment of an early and disabling symptom. Neurology. 2011;76:953-9 pubmed publisher
    ..To identify the prevalence and severity of fatigue and predicting factors for severe fatigue in autosomal dominant spinocerebellar ataxia (SCA)...
  36. OZ G, Hutter D, Tkac I, Clark H, Gross M, Jiang H, et al. Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status. Mov Disord. 2010;25:1253-61 pubmed publisher
    ..These data demonstrate that (1)H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients...
  37. Lirng J, Wang P, Chen H, Soong B, Guo W, Wu H, et al. Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy. PLoS ONE. 2012;7:e47925 pubmed publisher
    ..In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C).
  38. Thiffault I, Dicaire M, Tetreault M, Huang K, Demers Lamarche J, Bernard G, et al. Diversity of ARSACS mutations in French-Canadians. Can J Neurol Sci. 2013;40:61-6 pubmed
    ..The identification of Quebec ARSACS cases without two known SACS mutation led to the development of a multi-modal genomic strategy to uncover mutations in this large gene and explore phenotype variability...
  39. Pyle A, Griffin H, Yu Wai Man P, Duff J, Eglon G, Pickering Brown S, et al. Prominent sensorimotor neuropathy due to SACS mutations revealed by whole-exome sequencing. Arch Neurol. 2012;69:1351-4 pubmed
    ..Whole-exome sequencing rapidly defined the genetic cause of the disorder, expanding the clinical phenotype associated with SACS mutations to include a severe sensorimotor neuropathy. ..
  40. Prodi E, Grisoli M, Panzeri M, Minati L, Fattori F, Erbetta A, et al. Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series. Eur J Neurol. 2013;20:138-46 pubmed publisher
    ..The disease, first described in Canadian families from Québec, is characterized by cerebellar ataxia, pyramidal tract involvement and peripheral neuropathy...
  41. Perkins E, Clarkson Y, Sabatier N, Longhurst D, Millward C, Jack J, et al. Loss of beta-III spectrin leads to Purkinje cell dysfunction recapitulating the behavior and neuropathology of spinocerebellar ataxia type 5 in humans. J Neurosci. 2010;30:4857-67 pubmed publisher
  42. Matilla Dueñas A, Corral Juan M, Volpini V, Sanchez I. The spinocerebellar ataxias: clinical aspects and molecular genetics. Adv Exp Med Biol. 2012;724:351-74 pubmed publisher
    b>Spinocerebellar ataxias (SCAs) are a highly heterogeneous group of inherited neurological disorders, based on clinical characterization alone with variable degrees of cerebellar ataxia often accompanied by additional cerebellar and ..
  43. OZ G, Nelson C, Koski D, Henry P, Marjanska M, Deelchand D, et al. Noninvasive detection of presymptomatic and progressive neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J Neurosci. 2010;30:3831-8 pubmed publisher
    ..These data demonstrate that presymptomatic and progressive neurodegeneration in SCA1 can be noninvasively monitored using MRS...
  44. Mitsumura K, Hosoi N, Furuya N, Hirai H. Disruption of metabotropic glutamate receptor signalling is a major defect at cerebellar parallel fibre-Purkinje cell synapses in staggerer mutant mice. J Physiol. 2011;589:3191-209 pubmed publisher
    ..These results suggest that disruption of mGluR signalling at PF-PC synapses is one of the major synaptic defects in sg/sg mice and may manifest itself in SCA1 pathology...
  45. LORENZO D, Li M, Mische S, Armbrust K, Ranum L, Hays T. Spectrin mutations that cause spinocerebellar ataxia type 5 impair axonal transport and induce neurodegeneration in Drosophila. J Cell Biol. 2010;189:143-58 pubmed publisher
  46. Sułek Piatkowska A, Zdzienicka E, Raczyńska Rakowicz M, Krysa W, Rajkiewicz M, Szirkowiec W, et al. The occurrence of spinocerebellar ataxias caused by dynamic mutations in Polish patients. Neurol Neurochir Pol. 2010;44:238-45 pubmed
    Autosomal dominant spinocerebellar ataxias (SCAs) belong to a group of neurodegenerative disorders usually of adult age at onset...
  47. Vig P, Wei J, Shao Q, Lopez M, Halperin R, Gerber J. Suppression of calbindin-D28k expression exacerbates SCA1 phenotype in a disease mouse model. Cerebellum. 2012;11:718-32 pubmed publisher
    ..Our study provides further evidence for a critical role of CaB in SCA1 pathogenesis, which may help identify new therapeutic targets to treat SCA1 or other cerebellar ataxias...
  48. Hourez R, Servais L, Orduz D, Gall D, Millard I, de Kerchove d Exaerde A, et al. Aminopyridines correct early dysfunction and delay neurodegeneration in a mouse model of spinocerebellar ataxia type 1. J Neurosci. 2011;31:11795-807 pubmed publisher
  49. Wang J, Shen L, Lei L, Xu Q, Zhou J, Liu Y, et al. Spinocerebellar ataxias in mainland China: an updated genetic analysis among a large cohort of familial and sporadic cases. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36:482-9 pubmed publisher
    ..To undertake an updated genetic spectrum analysis in patients with hereditary spinocerebellar ataxia (SCA) in mainland China...
  50. Van Damme P, Veldink J, van Blitterswijk M, Corveleyn A, van Vught P, Thijs V, et al. Expanded ATXN2 CAG repeat size in ALS identifies genetic overlap between ALS and SCA2. Neurology. 2011;76:2066-72 pubmed publisher
    ..Intermediate CAG repeat expansions in ataxin 2 (ATXN2), the causative gene of spinocerebellar ataxia type 2 (SCA2), have been implicated in sporadic ALS. We studied ATXN2 in a large cohort of patients with sporadic and familial ALS...
  51. Tsou W, Soong B, Paulson H, Rodriguez Lebron E. Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6. Neurobiol Dis. 2011;43:533-42 pubmed publisher
    ..These results lend support to the preclinical development of SIS-RNAi as a potential therapy for SCA6 and other dominantly inherited diseases...
  52. Ikeda Y, Nagai M, Kurata T, Yamashita T, Ohta Y, Nagotani S, et al. Comparisons of acoustic function in SCA31 and other forms of ataxias. Neurol Res. 2011;33:427-32 pubmed publisher
    ..To investigate whether acoustic impairment can be one of the characteristic extracerebellar symptoms in sporadic and hereditary ataxias including spinocerebellar ataxia type 31 (SCA31)...
  53. Janer A, Werner A, Takahashi Fujigasaki J, Daret A, Fujigasaki H, Takada K, et al. SUMOylation attenuates the aggregation propensity and cellular toxicity of the polyglutamine expanded ataxin-7. Hum Mol Genet. 2010;19:181-95 pubmed publisher
    ..Our results demonstrate an influence of SUMOylation on the multistep aggregation process of ATXN7 and implicate a role for ATXN7 SUMOylation in SCA7 pathogenesis...