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

• Published in: Russian journal of genetics Vol. 58; no. 9; pp. 1145 - 1153
• Main Authors: Khidiyatova, I. M., Saifullina, E. V., Karunas, A. S., Akhmetgaleyeva, A. F., Kutlubaeva, R. F., Smakova, L. A., Lobov, S. L., Polyakov, A. V., Shchagina, O. A., Kadnikova, V. A., Ryzhkova, O. P., Magzhanov, R. V., Khusnutdinova, E. K.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-09-2022
• Subjects: Animal Genetics and Genomics; Biomedical and Life Sciences; Biomedicine; Human Genetics; Microbial Genetics and Genomics; mutations; NGS; hereditary spastic paraplegia; MLPA; Republic of Bashkortostan; gene
• ISSN: 1022-7954; 1608-3369
• DOI: 10.1134/S1022795422090113

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.