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Spinocerebellar ataxia 1: case and cohort-based studies in India


Affiliations
1 Manipal University, Manipal 576 104
2 National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bengaluru 560 065, India
 

Spinocerebellar ataxia 1 (SCA1) is a late-onset neurodegenerative disease caused by CAG (coding for glutamine) repeat expansions or polyglutamine (polyQ) aggregates in the ATXN1 gene. Apart from the causative CAG repeat expansions in the ATXN1 locus, environment and ethnicity have been hypothesized to affect clinical variability. This review brings together studies on SCA1 conducted in India and explores disease heterogeneity within the Indian population in general and within a cohort of SCA1 individuals in a South Indian village. The studies support existence of genetic factors in addition to CAG repeat sizes that are likely to influence SCA1 progression.

Keywords

Cohort studies, clinical variability, heterogeneity, genetic factors, neurodegenerative disease.
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  • Durr, A., Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol., 2010, 9, 885–894.

  • Zoghbi, H. Y. and Orr, H. T., Glutamine repeats and neurodegeneration. Annu. Rev. Neurosci., 2000, 23, 217–247.

  • Banfi, S., Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nature Genet., 1994, 7, 513–520.

  • Menon, R. P., The role of interruptions in polyQ in the pathology of SCA1. PLoS Genet., 2013, 9, e1003648.

  • Chung, M., Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I.Nature Genet., 1993, 5, 254–258.

  • Quan, F., A novel CAG repeat configuration in the SCA1 gene: implications for the molecular diagnostics of spinocerebellar ataxia type 1. Hum. Mol. Genet., 1995, 4, 2411–2413.

  • Rüb, U., Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7.Prog. Neurobiol., 2013, 104, 38–66.

  • Matilla-Dueñas, A., Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. Cerebellum, 2008, 7, 106–114.

  • Whaley, N. R., Autosomal dominant cerebellar ataxia type I: a review of the phenotypic and genotypic characteristics. Orphanet J. Rare Dis., 2011, 6, 33.

  • Basu, P., 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.

  • Sinha, K. K., Autosomal dominant cerebellar ataxia: SCA2 is the most frequent mutation in eastern India. J. Neurol. Neurosurg.Psychiatry, 2004, 75, 448–452.

  • Saleem, Q., 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.

  • Mittal, U., Insights into the mutational history and prevalence of SCA1 in the Indian population through anchored polymorphisms.Hum. Genet., 2005, 118, 107–114.

  • Krishna, N., SCA 1, SCA 2 & SCA 3/MJD mutations in ataxia syndromes in southern India. Indian J. Med. Res., 2007, 126, 465–470.

  • Sharma, S., Analysis of autosomal dominant spinocerebellar ataxia type 1 in an extended family of central India. Indian J.Hum. Genet., 2012, 18, 299–304.

  • Jacobi, H., Biological and clinical characteristics of individuals at risk for spinocerebellar ataxia types 1, 2, 3, and 6 in the longitudinal RISCA study: analysis of baseline data. Lancet Neurol., 2013,12, 650–658.

  • Ashizawa, T., Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J. Rare Dis., 2013, 8, 177.

  • Bryer, A., The hereditary adult-onset ataxias in South Africa.J. Neurol. Sci., 2003, 216, 47–54.

  • Kumaran, D., Genetic characterization of spinocerebellar ataxia 1 in a South Indian cohort. BMC Med. Genet., 2014, 15, 114.

  • Orr, H. T., Cell biology of spinocerebellar ataxia. J. Cell Biol., 2012, 197, 167–177.

  • Tsai, C.-C., Ataxin 1, a SCA1 neurodegenerative disorder protein, is functionally linked to the silencing mediator of retinoid and thyroid hormone receptors. Proc. Natl. Acad. Sci. USA, 2004, 101,4047–4052.

  • Yue, S., The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract. Hum. Mol. Genet., 2001, 10, 25–30.

  • Matilla-Dueñas, A., Cellular and molecular pathways triggering neurodegeneration in the spinocerebellar ataxias. Cerebellum, 2010, 9, 148–166.

  • Gehrking, K. M., Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum. Mol. Genet., 2011, 20, 2204–2212.

  • Cvetanovic, M., The role of LANP and ataxin 1 in E4F-mediated transcriptional repression. EMBO Rep., 2007, 8, 671–677.

  • Okazawa, H., Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron, 2002, 34, 701–713.

  • Yue, S., The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract. Hum. Mol. Genet., 2001, 10, 25–30.

  • Ju, H., Beyond the glutamine expansion: influence of posttranslational modifications of ataxin-1 in the pathogenesis of spinocerebellar ataxia type 1. Mol. Neurobiol., 2014; doi:10.1007/s12035-014-8703-z

  • Lin, X., Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1. Nature Neurosci.,2000, 3, 157–163.

  • Serra, H. G., Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice. Hum. Mol.Genet., 2004, 13, 2535–2543.

  • Cvetanovic, M., Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1. Nature Med., 2011, 17, 1445–1447.

  • Goldfarb, L. G., Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann. Neurol., 1996, 39, 500–506.

  • Agarwal, R., Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS ONE, 2014, 9, e114745.

  • Tamang, R., Complex genetic origin of Indian populations and its implications. J. Biosci., 2012, 37, 911–919.

  • Basu, A., Ethnic India: a genomic view, with special reference to peopling and structure. Genome Res., 2003, 13, 2277–2290.

  • Majumder, P. P., Ethnic populations of India as seen from an evolutionary perspective. J. Biosci., 2001, 26, 533–545.

  • Ranum, L. P., Molecular and clinical correlations in spinocerebellar ataxia type I: evidence for familial effects on the age at onset.Am. J. Hum. Genet., 1994, 55, 244–252.

  • Rengaraj, R., High prevalence of spinocerebellar ataxia type 1 in an ethnic Tamil community in India. Neurol. India, 2005, 53, 308–310.

  • DeStefano, A. L., PARK3 influences age at onset in Parkinson disease: a genome scan in the GenePD study. Am. J. Hum. Genet., 2002, 70, 1089–1095.

  • Lee, J. H., Age-at-onset linkage analysis in Caribbean Hispanics with familial late-onset Alzheimer’s disease. Neurogenetics, 2008, 9, 51–60.

  • Guerreiro, R. J., Exome sequencing reveals an unexpected genetic cause of disease: NOTCH3 mutation in a Turkish family with Alzheimer’s disease. Neurobiol. Aging, 2012, 33, 1008.e17–23.

  • Jin, S. C., Pooled-DNA sequencing identifies novel causative variants in PSEN1, GRN and MAPT in a clinical early-onset and familial Alzheimer’s disease Ibero-American cohort. Alzheimers Res. Ther., 2012, 4, 34.


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  • Spinocerebellar ataxia 1: case and cohort-based studies in India

Abstract Views: 381  |  PDF Views: 135

Authors

Dhanya Kumaran
Manipal University, Manipal 576 104
Gaiti Hasan
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bellary Road, Bengaluru 560 065, India

Abstract


Spinocerebellar ataxia 1 (SCA1) is a late-onset neurodegenerative disease caused by CAG (coding for glutamine) repeat expansions or polyglutamine (polyQ) aggregates in the ATXN1 gene. Apart from the causative CAG repeat expansions in the ATXN1 locus, environment and ethnicity have been hypothesized to affect clinical variability. This review brings together studies on SCA1 conducted in India and explores disease heterogeneity within the Indian population in general and within a cohort of SCA1 individuals in a South Indian village. The studies support existence of genetic factors in addition to CAG repeat sizes that are likely to influence SCA1 progression.

Keywords


Cohort studies, clinical variability, heterogeneity, genetic factors, neurodegenerative disease.

References





DOI: https://doi.org/10.18520/cs%2Fv109%2Fi5%2F889-892