Abstract
Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders with a predominant lesion of the pyramidal tract. To date, mutations responsible for the disease have been identified in more than 70 genetic loci. The main causes of HSP development are mutations in the SPAST gene, but major mutations are rare for this disease. Study of HSP patients from 63 unrelated families from the Bashkortostan Republic (BR) identified the c.283delG (p.Ala95Profs*66) mutation in the SPAST gene in families of Tatar ethnicity with a high frequency. In the general cohort of unrelated patients from the Bashkortostan Republic, its frequency was 19%, and in the cohort of Tatar patients, it was 44%. HSP was found to be inherited in an autosomal dominant manner in all families with this mutation. The clinical symptoms of the disease in most of these families corresponded to the uncomplicated phenotype, typical of the SPG4 form of HSP.
Similar content being viewed by others
REFERENCES
Harding, A.E., Classification of the hereditary ataxias and paraplegias, Lancet, 1983, vol. 321, no. 8334, pp. 1151—1155.
Magzhanov, R.V., Saifullina, E.V., Idrisova, R.F., et al., Epidemiology of hereditary spastic paraplegias in Bashkortostan Republic, Med. Genet., 2013, no. 7, pp. 12—16.
Novarino, G., Fenstermaker, A.G., and Zaki, M.S., Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders, Science, 2014, vol. 343, no. 6170, pp. 506—511. https://doi.org/10.1126/science.1247363
Klebe, S., Stevanin, G., and Depienne, C., Clinical and genetic heterogeneity in hereditary spastic paraplegias: from SPG1 to SPG72 and still counting, Rev. Neurol., 2015, vol. 171, no. 6, pp. 505—530. https://doi.org/10.1016/j.neurol.2015.02.017
Fink, J.K., Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms, Acta Neuropathol., 2013, vol. 126, no. 3, pp. 307—328. https://doi.org/10.1007/s00401-013-1115-8
Fonknechten, N., Mavel, D., Byrne, B., et al., Spectrum of SPG4 mutations in autosomal dominant spastic paraplegia, Hum. Mol. Genet., 2000, vol. 9, no. 4, pp. 637—644.
Akhmetgaleeva, A.F., Khidiyatova, I.M., Saifullina, E.V., et al., Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia, Russ. J. Genet., 2016, vol. 52, no. 6, pp. 603—607. https://doi.org/10.1134/S1022795416060028
Akhmetgaleeva, A.F., Khidiyatova, I.M., Saifullina, E.V., et al., Clinical case of sporadic spastic paraplegia with a new mutation in the SPAST gene, Med. Genet., 2016, vol. 15, no. 7, pp. 11—13.
Lindsey, J.C., Lusher, M.E., McDermott, C.J., et al., Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis, J. Med. Genet., 2000, vol. 37, no. 10, pp. 759—765.
Hentati, A., Deng, H.X., Zhai, H., et al., Novel mutations in spastin gene and absence of correlation with age at onset of symptoms, Neurology, 2000, vol. 55, no. 9, pp. 1388—1390.
Basri, R.1., Yabe, I., Soma, H., et al., Four mutations of the spastin gene in Japanese families with spastic paraplegia, J. Hum. Genet., 2006, vol. 51, no. 8, pp. 711—715. https://doi.org/10.1007/s10038-006-0412-7
Lumb, J.H., Connell, J.W., Allison, R., and Reid, E., The AAA ATPase spastin links microtubule severing to membrane modelling, Biochim. Biophys. Acta, 2012, vol. 1823, no. 1, pp. 192—197. https://doi.org/10.1016/j.bbamcr.2011.08.010
Guizetti, J., Schermelleh, L., Mäntler, J., et al., Cortical constriction during abscission involves helices of ESCRT-III-dependent filaments, Science, 2011, vol. 331, no. 6024, pp. 1616—1620. https://doi.org/10.1126/science.1201847
Allison, R.1., Lumb, J.H., Fassier, C., et al., An ESCRT—spastin interaction promotes fission of recycling tubules from the endosome, J. Cell Biol., 2013, vol. 202, no. 3, pp. 527—543. https://doi.org/10.1083/jcb.201211045
White, S.R. and Lauring, B., AAA+ ATPases: achieving diversity of function with conserved machinery, Traffic, 2007, vol. 8, no. 12, pp. 1657—1667. https://doi.org/10.1111/j.1600-0854.2007.00642.x
Park, S.H., Zhu, P.P., Parker, R.L., and Blackstone, C., Hereditary spastic paraplegia proteins REEP1, spastin, and atlastin-1 coordinate microtubule interactions with the tubular ER network, J. Clin. Invest., 2010, vol. 120, no. 4, pp. 1097—1110. https://doi.org/10.1172/JCI40979
Blackstone, C., O’Kane, C.J., and Reid, E., Hereditary spastic paraplegias: membrane traffic and the motor pathway, Nat. Rev. Neurosci., 2011, vol. 12, no. 1, pp. 31—42. https://doi.org/10.1038/nrn2946
Blackstone, C., Cellular pathways of hereditary spastic paraplegia, Annu. Rev. Neurosci., 2012, vol. 35, pp. 25—47. https://doi.org/10.1146/annurev-neuro-062111-150400
Evans, K.J., Gomes, E.R., Reisenweber, S.M., et al., Linking axonal degeneration to microtubule remodeling by spastin-mediated microtubule severing, J. Cell. Biol., 2005, vol. 168, no. 4, pp. 599—606.
Errico, A., Ballabio, A., and Rugarli, E.I., Spastin, the protein, mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics, Hum. Mol. Genet., 2002, vol. 11, no. 2, pp. 153—163.
Solowska, J.M. and Baas, P.W., Hereditary spastic paraplegia SPG4: what is known and not known about the disease, Brain, 2015, pp. 2471—2484.
Rebbapragada, I. and Lykke-Andersen, J., Execution of nonsense-mediated mRNA decay: what defines a substrate?, Curr. Opin. Cell Biol., 2009, vol. 21, no. 3, pp. 394—402. https://doi.org/10.1016/j.ceb.2009.02.007
Lykke-Andersen, S. and Jensen, T.H., Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes, Nat. Rev. Mol. Cell Biol., 2015, vol. 16, no. 11, pp. 665—677. https://doi.org/10.1038/nrm4063
Burger J., Fonknechten N., Hoeltzenbein M. et al. Hereditary spastic paraplegia caused by mutations in the SPG4 gene, Eur. J. Hum. Genet. 2000, vol. 8, no. 10, pp. 771—776. https://doi.org/10.1038/sj.ejhg.5200528
Solowska, J.M., Rao, A.N., and Baas, P.W., Truncating mutations of SPAST associated with hereditary spastic paraplegia indicate greater accumulation and toxicity of the M1 isoform of spastin, Mol. Biol. Cell., 2017, vol. 28, no. 13, pp. 1728—1737. https://doi.org/10.1091/mbc.E17-01-0047
de Bot, S.T., Elzen, R.T., and Mensenkamp, A.R., Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations, J. Neurol. Neurosurg. Psychiatry, 2010, vol. 81, no. 10, pp. 1073—1078. https://doi.org/10.1136/jnnp.2009.201103
Sauter, S., Miterski, B., Klimpe, S., et al., Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia, Hum. Mutat., 2002, vol. 20, no. 2, pp. 127—132. https://doi.org/10.1002/humu.10105
Magariello, A., Muglia, M., Patitucci, A., et al., Novel spastin (SPG4) mutations in Italian patients with hereditary spastic paraplegia, Neuromusc. Disord., 2006, vol. 16, no. 6, pp. 387—390. https://doi.org/10.1016/j.nmd.2006.03.009
Crippa, F., Panzeri, C., Martinuzzi, A., et al., Eight novel mutations in SPG4 in a large sample of patients with hereditary spastic paraplegia, Arch. Neurol., 2006, vol. 5, pp. 750—755. https://doi.org/10.1001/archneur.63.5.750
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interests. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The studies were approved by the Bioethics Committee of Institute of Biochemistry and Genetics, Ufa Federal Research Center, Russian Academy of Sciences. Informed consent was obtained from all individual participants involved in the study.
Additional information
Translated by A. Kashevarova
Rights and permissions
About this article
Cite this article
Khidiyatova, I.M., Akhmetgaleyeva, A.F., Saifullina, E.V. et al. Major Mutation in the SPAST Gene in Patients with Autosomal Dominant Spastic Paraplegia from the Republic of Bashkortostan. Russ J Genet 55, 259–262 (2019). https://doi.org/10.1134/S1022795419020091
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795419020091