Phenotypic features of a Russian family with spinocerebellar ataxia type 6 from Khabarovsk Krai

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Abstract

The article presents a familial case of spinocerebellar ataxia type 6, consisting of 7 people across 4 generations from a mixed marriage of Yakut, Even, and Russian ethnicities, living in Khabarovsk Krai. The mutant allele of the CACNA1A gene had 27 stable CAG repeats in all patients (normal is <18 CAG repeats), while the normal allele had 13 CAG repeats. Clinical features included rapidly progressing cerebellar ataxia in males (0.96–9.00 points per year on the SARA scale); presence of psychological disorders in the form of alcoholism, early-onset binge drinking, completed suicidal behaviors; life expectancy reduced in 2 patients to 27 and 36 years.

 

About the authors

Tatyana N. Proskokova

Far-Eastern State Medical University

Author for correspondence.
Email: proskokova2011@yandex.ru
Russian Federation, Khabarovsk

Dmitry V. I.

Far-Eastern State Medical University

Email: proskokova2011@yandex.ru
Russian Federation, Khabarovsk

Natal’ya B. Serdyuk

Far-Eastern State Medical University

Email: proskokova2011@yandex.ru
Russian Federation, Khabarovsk

Natal’ya Yu. Abramycheva

Research Center of Neurology

Email: proskokova2011@yandex.ru
Russian Federation, Moscow

References

  1. Casey H.L., Gomez C.M. Spinocerebellar ataxia type 6. Gene Reviews. Seattle, 1998. PMID: 20301319.
  2. Guinti P., Mantuano E., Frontali M. et al. Molecular mechanism of spinocerebellar ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation. Front Cell Neurosci. 2015; 9: 36. doi: 10.3389/fncel. 2015.00036. PMID: 25762895.
  3. Coarelli G., Brice A., Durr A. Recent advances in understanding dominant spinocerebellar ataxias from clinical and genetic points of view. F100 Res. 2018; 7: F1000FacultyRev-1781. doi: 10.12688/f1000research.15788.1. PMID: 30473770.
  4. Wiethoff S., O’Connor E., Haridy N.A. et al. Sequencing analysis of the SCA6 CAG expansion excludes an influence of repeat interruptions on disease onset. J Neurol Neurosurg Psychiatry. 2018; 89(11): 1226–1227. doi: 10.1136/jnnp-2017-317253. PMID: 29367260.
  5. Bavassano C., Eigentlera A., Stanika R. et al. Bicistronic CACNA1A gene expression in neurons derived from spinocerebellar ataxia type 6 patients-induced pluripotent stem cells. Stem Cells Dev. 2017; 26(22): 1612–1625. doi: 10.1089/scd.2017.0085. PMID: 28946818.
  6. Paulson H.L., Shakkottai V.G., Clark H.B., Orr H.T. Polyglutamine spinocerebellar ataxias — from genes to potential treatmens. Nat Rev Neurosci. 2017; 18(10): 613–626. doi: 10.1038/nm.2017.92. PMID: 28855740.
  7. Sakakibara R., Tateno F., Kishi M. et al. Genetic screening for spinocerebellar ataxia genes in a Japanese single hospital cohort. J Mov Disord. 2017; 10(3): 116–122. doi: 10.14802/jmd.170.11. PMID: 28782341.
  8. Solodkin A., Gomez C.M. Spinocerebellar ataxia type 6. Handb Clin Neurol. 2012; 103: 461–473. doi: 10.1016/B978-0-444-51892-7.00029-2. PMID: 21827907.
  9. Soga K., Ishikawa K., Furuya T. et al. Gene dosage effect in spinocerebellar ataxia type 6 homozygotes: a clinical and neuropathological study. J Neurol. Sci. 2017; 15(373): 321–328. doi: 10.1016/j.jns.2016.12.051. PMID: 28131213.
  10. Takahashi H., Ishikawa K., Tsutsumi T. et al. A clinical and genetic study in a large cohort of patients with spinocerebellar ataxia type 6. J Hum Genet. 2004; 49: 256–264. doi: 10.1007/s10038-004-0142-7. PMID: 15362569
  11. Kuo P.H., Gan S.R., Wang J. et al. Dystonia and ataxia progression in spinocerebellar ataxias. Parkinsonism Relat. Disord. 2017; 45: 75–80. doi: 10.1016/j.parkreldis.2017.10.1007. PMID: 29089256.
  12. Chen S.J., Lee N.C., Chien Y.H. et al. Heterogeneous nonataxic patients of spinocerebellar ataxia in Taiwanese population. Brain Behav. 2019; 9(10): e01444. doi: 10.1002/brb3.1414. PMID: 31523939.
  13. Lay R.Y., Tomishon D., Figueroa K.P. et al. Tremor in the degenerative cerebellum: towards the understanding of brain circuity for tremor. Cerebellum. 2019; 18(3): 519–526. doi: 10.1007/s12311-019-01016-6. PMID: 30830673.
  14. Schols L., Linnemann C., Globas C. Electrophysiology in spinocerebellar ataxias: spread of disease and characteristic findings. Cerebellum. 2008; 7: 198–203. doi: 10.1007/s12311-008-0024-1. PMID: 18418678.
  15. Yun J.Y., Kim J.M., Kim H.J. et al. SCA6 presenting with young-onset parkinsonism without ataxia. Mov Disord. 2012; 27(8): 1067–1068. doi: 10.1002/mds.241077. PMID: 22605520.
  16. Takeshima S., Takeda I., Kobatake K. et al. SCA6 presenting parkinsonism without ataxia — a case report. Rinsho Shinkeigaku. 2015; 55(4): 243–247. doi: 10.5692/clinicalneurol.55.243. PMID: 25904253.
  17. Globas C., du Montcel S. T., Balik et al. Early symptoms spinocerebellar ataxias type 1, 2, 3 and 6. Mov Disord. 2008; 23: 2232–2238. doi: 10.1002/mds.22288. PMID: 18759344.
  18. Pereira L., Airan R.D., Fishman A. et al. Resting-state functional connectivity and cognitive dysfunction correlations in spinocerebellar ataxia type 6 (SCA6). Hum Brain Mapp. 2017; 38(6): 3001–3010. doi: 10.1002/hbm.23568. PMID: 28295805.
  19. Tamura L., Takei A., Hamada S. et al. Cognitive dysfunction in patients with spinocerebellar ataxia type 6. J Neurol. 2017; 264(2): 260–267. doi: 10.1007/900415-016-8344-4. PMID: 27878440.
  20. Indelicato E., Nachbauer W., Karner E. et al. The neuropsychiatric phenotype in CACNA1A mutations: a retrospectivesingle center study and review of the literature. Eur J Neurol. 2019; 26(1): 66–67. doi: 10.1111/ene.13765. PMID: 30063100.
  21. Craig K., Takiyama Y., Soong B. W. et al. Pathogenic expansions of the SCA6 locus are associated with a common CACNA1A haplotype across the globe: founder effect or predisposing chromosome? Eur J Hum Genet. 2008; 16: 841–847. doi: 10.1038/ejhg.2008.20. PMID: 18285829.
  22. Novikova L.V. [Clinical and genetic analysis of type 6 spinocerebellar ataxia: dis. ... Cand. med. sci.]. Moscow, 2002.S. 108.
  23. Mingarova E.Z. [Clinical-epidemiological and molecular-genetic study of progressive spinocerebellar ataxias in the Republic of Bashkortostan: dis. ... Cand. med. sci.]. Moscow, 2009.S. 171.
  24. Pastor P.D.H., Du X., Fazal S., Davies A.N. Targeting the CACNA1A IRES as a treatment for spinocerebellar ataxia type 6. Cerebellum. 2018; 17(1): 72–77. doi: 10.1007/s12311-018-0917-6. PMID: 29374372.
  25. Govek E.E., Hatten M.E. Tag-team genetics of spinocerebellar ataxia type 6. Neuron. 2019; 102: 707–709. doi: 10.1016/j.neuron.2019.04.041. PMID: 31121118.

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Copyright (c) 2021 Proskokova T.N., I. D.V., Serdyuk N.B., Abramycheva N.Y.

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