The role of spastin and paraplegin genes in primary progressive multiple sclerosis

Burak Çopuroğlu; Ali Ulvi Uca; Ayse Gul Zamani; Mahmut Selman Yıldırım; Mustafa Altaş; Betül Okur Altındaş

doi:10.55697/tnd.2024.12

Burak Çopuroğlu¹, Ali Ulvi Uca¹, Ayse Gul Zamani², Mahmut Selman Yıldırım², Mustafa Altaş¹, Betül Okur Altındaş²

¹Department of Neurology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye
²Department of Medical Genetics, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Türkiye

Keywords: Hereditary spastic paraplegia, multipl sclerosis, paraplegin (SPG7), spastin (SPG4).

Abstract

Objectives: This study aimed to detect the presence of mutations in the spastin (SPG4) and paraplegin (SPG7) genes in patients with primary progressive multiple sclerosis (PPMS) to determine the role of hereditary spastic paraplegia (HSP) genes on the susceptibility to PPMS, clinical course, and severity and to reveal its potential role on motor pathways leading to spastic paraparesis clinic.

Patients and methods: The descriptive study was conducted with 25 patients with PPMS. The patients were divided into two groups: those presenting with (n=16; 8 males, 8 females; mean age: 47.2±8.4 years; range, 32 to 58 years) and without (n=9; 5 males, 4 females; mean age: 42.8±5.8 years; range, 34 to 49 years) spastic paraparesis. The SPG4 and SPG7 genes from the purified DNAs, which were isolated from blood samples, were sequenced to include all exons and introns. The variations detected as a result of the analysis were evaluated in terms of the suitability of the reading parameters. The frequency of variants in populations and the number of homozygous variants in individuals were analyzed with the gnomAD (Genome Aggregation Database). Of the detected variants, only pathogenic and possibly pathogenic variants that could be clinically associated were reported.

Results: In the genotyping of the two groups with PPMS, both with and without spastic paraparesis, no pathogenic or probable pathogenic variant was observed in terms of SPG4 and SPG7 genes.

Conclusion: We found no evidence that the SPG4 and SPG7 genes were involved in the pathogenesis, clinical course, and severity of PPMS. However, the question of what kind of effects these genes have on susceptibility to multiple sclerosis and the course remains unclear.

Cite this article as: Çopuroğlu B, Uca AU, Zamani AG, Yıldırım MS, Altaş M, Okur Altındaş B. The role of spastin and paraplegin genes in primary progressive multiple sclerosis. Turk J Neurol 2024;30(4):236-243. doi: 10.55697/tnd.2024.12.