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Analysis of ATL1 Gene Mutations and Clinical Features of the Disease Course in Patients with Hereditary Spastic Paraplegia

  • HUMAN GENETICS
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Abstract

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders with a predominant lesion of the pyramidal tract. The autosomal dominant form of SPG3A, associated with mutations in the ATL1 gene, is one of the most common forms of HSP in European populations. Analysis of the ATL1 gene was performed in 63 unrelated families with HSP from the Republic of Bashkortostan. Two pathogenic variants were identified: one patient had a duplication of the entire third exon, and seven patients from three unrelated families had a missense mutation c.1246C>T (p.Arg416Cys). The frequency of SPG3A among unrelated patients in Bashkortostan was 6.3%. In one of the examined families, the origin of the c.1246C>T de novo mutation was established. The clinical symptoms of the disease in most cases correspond to uncomplicated HSP occurring in a mild form. Intrafamilial differences in clinical manifestations of the disease, including in identical twins, were revealed. The age of manifestation in the majority of examined patients ranged from 10 to 50 years.

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ACKNOWLEDGMENTS

For the study, the equipment of the Center for Collective Use Biomika (Department of Biochemical Research Methods and Nanobiotechnology of the Republican Center for Collective Use Agidel) and UNU KODINK was used. The DNA samples for the study were taken from the “Collection of Human Biological Materials” of the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences, supported by the Program of Bioresource Collections of FASO of Russia (agreement no. 007-030164/2).

Funding

This work was carried out within the framework of the State Order of the Ministry of Education and Science of the Russian Federation (no. АААА-А16-116020350032-1), with partial financial support from St. Petersburg State University (project no. 93025749), a grant of the Russian Foundation for Basic Research (no. 17-44-020951), and a Megagrant of the Government of the Russian Federation (agreement no. 075-15-2021-595).

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Authors and Affiliations

  1. Institute of Biochemistry and Genetics—Subdivision of the Ufa Federal Research Center, Russian Academy of Sciences, 450054, Ufa, Russia

    I. M. Khidiyatova, A. S. Karunas, L. A. Smakova, S. L. Lobov & E. K. Khusnutdinova

  2. Bashkir State University, 450076, Ufa, Russia

    I. M. Khidiyatova, A. S. Karunas & E. K. Khusnutdinova

  3. Saint Petersburg State University, 199034, St. Petersburg, Russia

    I. M. Khidiyatova, A. S. Karunas & E. K. Khusnutdinova

  4. Bashkir State Medical University, 450000, Ufa, Russia

    E. V. Saifullina, A. F. Akhmetgaleyeva, R. F. Kutlubaeva & R. V. Magzhanov

  5. Medical Genetic Research Center, 115522, Moscow, Russia

    A. V. Polyakov, O. A. Shchagina, V. A. Kadnikova & O. P. Ryzhkova

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  1. I. M. Khidiyatova
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  2. E. V. Saifullina
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  4. A. F. Akhmetgaleyeva
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  5. R. F. Kutlubaeva
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  6. L. A. Smakova
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  7. S. L. Lobov
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  8. A. V. Polyakov
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  11. O. P. Ryzhkova
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  12. R. V. Magzhanov
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Correspondence to I. M. Khidiyatova.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in a study involving people comply with the ethical standards of the institutional and/or national committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards. The studies were approved by the bioethics committee of the Institute of Biochemistry and Genetics, Ufa Federal Research Center of the Russian Academy of Sciences.

Informed consent was obtained from each of the participants included in the study.

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Khidiyatova, I.M., Saifullina, E.V., Karunas, A.S. et al. Analysis of ATL1 Gene Mutations and Clinical Features of the Disease Course in Patients with Hereditary Spastic Paraplegia. Russ J Genet 58, 1145–1153 (2022). https://doi.org/10.1134/S1022795422090113

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  • DOI: https://doi.org/10.1134/S1022795422090113

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