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Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)


Goldfarb L.G., Platonov F.A.                                                                                                                                                                                                         PDF

Annotation. Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without targeted preventive measures.

Key words: Republic of Sakha (Yakutia), Autosomal dominant spinocerebellar ataxia type 1 (SCA1), ATXN1 gene, trinucleotide repeat expansion.

For citation: Goldfarb L.G., Platonov F.A. Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) // Siberian Research. 2019. 2 (2). P. 62 – 73.

Received July 12, 2019; accepted October 31, 2019; published December 1, 2019


About authors

Goldfarb Lev G., MD, PhD, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20852, USA,, e-mail:

Platonov Fyodor A., MD, PhD, Institute of Health, M.K. Ammosov North-Eastern Federal University, Yakutsk 677010, The Russian Federation, email:




  1. Goldfarb LG, Vasconcelos O, Platonov FA, Lunkes A, Kipnis V, Kononova S, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol. 1996;39(4):500–506.
  2. Koneva LA, Konev AV, Kucher AN. Simulation of the distribution of spinocerebellar ataxia type 1 in Yakut populations: model parameters and simulation results. Genetika (Russian). 2010; 46(7):990-99.
  3. Vladimirtsev VA, Nikitina RS, Renwick N, Ivanova AA, Danilova AP, Platonov FA, et al. Family clustering of Viliuisk encephalomyelitis in traditional and new geographic regions. Emerging Infectious Diseases.2007;13:1321-26.
  4. Lunkes A, Goldfarb LG, Platonov FA, Alexeev VP, Duenas-Barajas E, Gajdusek DC, Auberger G. Autosomal dominant spinocerebellar ataxia (SCA) in a Siberian founder population: assignment to the SCA1 locus. Experimental Neurology. 1994;126:310-12.
  5. Ranum LP, Chung MY, Banfi S, Bryer A, Schut LJ, Ramesar R, et al. Molecular and clinical correlations in spinocerebellar ataxia type 1: evidence for familial effects on the age at onset. Am J Hum Genet. 1994;55:244–52.
  6. Orr HT, Chung MY, Banfi S, Kwiatkowski TJ, Servadio A, Beaudet AL, et al. Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet. 1993;4(3):221–26.
  7. Banfi S, Servadio A, Chung MY, Kwiatkowski TJ Jr, McCall AE, Duvick LA, et al. Identification and characterization of the gene causing type 1 spinocerebellar ataxia. Nat Genet. 1994;7(4):513-20.
  8. Chung MY, Ranum LP, Duvick LA, Servadio A, Zoghbi HY, Orr HT. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet. 1993;5(3):254–58.
  9. Matilla A, Roberson ED, Banfi S, Morales J, Armstrong DL, Burright EN, et al. Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired-pulse facilitation. J Neurosci. 1998;18:5508–16.
  10. Jodice C, Malaspina P, Persichetri F, Novelletto A, Spadaro M, Giunti P, et al. Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia 1. Am J Hum Genet 1994; 54:959–965.
  11. Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci. 2007;30:575–621.
  12. Goldfarb LG, Chumakov MP, Рetrov PA, Fedorova NI, Gajdusek DC. Olivopontocerebellar atrophy in a large Iakut kinship in Eastern Siberia. Neurology. 1989;39:1527-30.
  13. Kononova S. K., Sidorova O. G., Fedorova S. A., Platonov F. A., Goldfarb L. G., Izhevskaya V. L., Khusnutdinova E. K. Ethical, legal and social problems regarding the use of genetic studies in Yakutia. Yakut Medical Journal 2009;2(26),86-88.
  14. Osakovsky V.L., Shatunov A.A., Platonov F.A., Goldfarb L.G. The age of the SCA1 chromosome in the Yakut population. Yakut Medical Journal 2004;2,63.
  15. Osakovsky V.L., Goldfarb L.G., Platonov F.A. On the origin of the SCA1 mutation in the Yakut population. Bulletin of the SB RAMS. 2004;1(111),103-4.
  16. Tikhonov D.G., Goldfarb L.G., Neustroeva T.S., Yakovleva N.V., Timofeev L.F., Lukan I.P., Platonov F.A. Analysis of the life expectancy and mortality of patients with spinocerebellar ataxia type 1. Topics of Social Hygiene and Health in Medical History. 2015;(6):31-4.
  17. Platonov FA, Tyryshkin K, Tikhonov DG, Neustroyeva TS, Sivtseva TM, Yakovleva NV, et al. Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1. Neurogenetics. 2016;17(3):179-185.
  18. Yakovleva N.V., Platonov F.A. Spinocerebellar ataxia type 1: a family with homozygous inheritance. Yakut Medical Journal. 2009; 2 (26),85-87.
  19. Goldfarb L.G., Vladimirtsev V.A., Renwick N.M., Platonov F.A. Viliuisk encephalomyelitis. Novosibirsk. 2014,p.1-254.
  20. Sambuughin N, Goldfarb LG, Sivtseva TM, Davydova TK, Vladimirtsev VA, Osakovskiy VL, et al. Adult-onset autosomal dominant spastic paraplegia linked to a GTPase-effector domain mutation of dynamin 2. BMC Neurol. 2015;15:223-35. doi: 10.1186/s12883-015-0481-3
  21. Crow JF. Some possibilities for measuring selection intensities in man. Hum Biol. 1958;30:1–13.
  22. Kononova SK, Sidorova OG, Fedorova SA, Platonov FA, Izhevskaya VL, Khusnutdinova EK. Bioethical issues in preventing hereditary diseases with late onset in the Sakha Republic (Yakutia). Int J Circumpolar Health (eCollection). 2014;73:25062.
  23. Sidorova OG, Kononova S.K., Stepanova S.K., Zakharova V.A., Fedorova S.A., Izhevskaya V.L., Khusnutdinova E.S. Prenatal diagnosis of spinocerebellar ataxia type 1 and myotonic dystrophy as part of genetic counseling in Yakutia. Yakut Medical Journal. 2009;2(26),64-66.
  24. Subramony SH, Ashizawa T. Spinocerebellar Ataxia Type 1. Pagon RA, et al., Editors. GeneReviews® , University of Washington, Seattle, WA. 2015 (
  25. Paradisi I, Ikonomu V, Arias S. Spinocerebellar ataxias in Venezuela: genetic epidemiology and their most likely ethnic descent. J Hum Genet. 2016;61(3):215-22.
  26. Rengaraj R, Dhanaraj M, Arulmozhi T, Chattopadhyay B, Battacharyya NP. High prevalence of spinocerebellar ataxia type 1 in an ethnic Tamil community in India. Neurol India. 2005;53:308–11.
  27. Sumathipala DS, Abeysekera GS, Jayasekara RW, Tallaksen CM, Dissanayake VH. Autosomal dominant hereditary ataxia in Sri Lanka. BMC Neurol. 2013;13:13–39.
  28. OnoderaY, AokiM, TsudaT, KatoH, NagataT, KameyaT, AbeK, Itoyama Y. High prevalence of spinocerebellar ataxia type 1 (SCA1) in an isolated region of Japan. J Neurol Sci. 2000;178:153–58.
  29. Velázquez Pérez L, Cruz GS, Santos Falcón N, Enrique Almaguer Mederos L, Escalona Batallan K. Molecular epidemiology of spinocerebellar ataxias in Cuba: insights into SCA2 founder effect in Holguin. Neurosci Lett. 2009;454:157–60
  30. Sobczak K, Krzyzosiak WJ. Patterns of CAG repeat interruptions in SCA1 and SCA2 genes in relation to repeat instability Hum Mutat. 2004;24(3):236-47.
  31. Schöls L, Amoridis G, Büttner T, Przuntek H, Epplen JT, Riess O. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol. 1997;42:924–32.
  32. Stevanin G, Durr A, Brice A. Clinical and molecular advances in autosomal dominant cerebellar ataxias: from genotype to phenotype and physiopathology. Eur J Hum Genet. 2000;8:4–18.
  33. Filla A, De Michele G, Campanella G, Perretti A, Santoro L, Serlenga L, et al. Autosomal dominant cerebellar ataxia type I. Clinical and molecular study in 36 Italian families including a comparison between SCA1 and SCA2 phenotypes. J Neurol Sci. 1996;142(1-2):140-47.
  34. Jacobi H, Bauer P, Giunti P, Labrum R, Sweeney MG, Charles P, Dürr A. The natural history of spinocerebellar ataxia type 1, 2, 3, and 6: a 2-year follow-up study. Neurology. 2011;77:1035–41.
  35. Frontali M, Sabbadini G, Novelletto A, Jodice C, Naso F, Spadaro M, et al. Genetic fitness in Huntington’s disease and spinocerebellar ataxia 1: a population genetics model for CAG repeat expansions. Ann Hum Genet. 1996;60:423–35.
  36. Khongsdier R. Population genetics in Northeast India: an overview. Khongsdier R (ed). Contemporary research in anthropology. New Delhi: Commonwealth Publishers. 2000, p.1-24.
  37. Kucher AN, Danilova AL, Koneva LA, Nogovitsyna AN. The structure of rural settlements of the Republic of Sakha (Yakutia): ethnic, gender and age composition and statistics of natural population. Genetiks (Russian). 2006; 42: 1718-1726.
  38. Tarskaya LA, Elchinova GI, Varzar AM, Shabrova E.V. Genetic and demographic structure of the Yakut population: rates of reproduction. Genetiks (Russian). 2002;38:985-91.
  39. Koneva LA, Konev AB, Kucher AN. Prediction of type 1 spinocerebellar ataxia prevalence in simulated Yakut populations. Yakutsk Medical Journal. 2009;2(26),83-6.
  40. Koneva LA, Konev AV, Kucher AN. Modeling the distribution of type I spinocerebellar ataxia in the Yakut population: model description. Genetiks (Russian). 2010,46 (3):417-24.


A note added after this review has been accepted for publication:

The authors became aware of a recent publication by Varlamova et al. (2018) on the discovery of Dentatorubral-pallidoluyisian atrophy (DRPLA) in five members of a Sakha family. This disease similarly to SCA1 is associated with an expansion of an uninterrupted CAG repeat in the ATN1 gene. And similarly, ataxia is the dominant clinical feature of DRPLA.


Varlamova MA, Nazarova PS, Ilyinova EA, Pavlova NI, Sidorova OG, Kononova SK, Solovyova NA, Dyakonova AT, Kurtanov XA. Clinical-genealogical and molecular-genetic  features of patients with spinocerebellar ataxia type 1 and dentatorubropallidoluyuisian atrophy in Yakutia. Current Problems of Science and Education. 2018; 6.


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Humanitarian Research
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of the English edition
Candidate of Philological Sciences, Associate Professor, Department of English Philology Institute of Foreign Phi-lology and Area Studies, North-Eastern Federal University

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