A Turkish Patient with Spastic Paraplegia Type 4 with a De Novo Missense Mutation in the SPAST Gene

Authors : Emine İkbal Atlı, Hakan Gurkan, Engin Atlı

Pages : 151-157

Doi:10.20515/otd.1594823

View : 40 | Download : 53

Publication Date : 2025-01-17

Article Type : Other Papers

Abstract :Spastic paraplegia type 4 is a common type of autosomal-dominant pure hereditary spastic paraplegia that is brought on by variations in the SPAST gene. In this investigation, the SPAST genotype and clinical phenotype of a Turkish SPG4 patient were analyzed in an effort to provide additional genetic evidence for the pathophysiology of HSP. The clinical data of the proband and his family members were collected. After complete genomic DNA was isolated from peripheral blood, whole-exome sequencing technology was used to identify genes and analyze the pathogenicity of variants. Variants suspected of being pathogenic were found. Within this family, Sanger sequencing was used for verification. The sequencing of SPAST revealed a de novo missense c.1496G > A (p.Arg499His) and missense MEFV c.2177T>C (p.Val726Ala) variants. The parents and paternal relatives did not have the SPAST mutation. De novo variants of the c.1496G > A mutation in SPAST can arise at notably high frequencies. We discussed the case of a Turkish patient and examined the clinical characteristics of patients with the p.Arg499His variation in SPAST that have been documented in the literature. There is growing evidence that the p.Arg499His missense mutation in SPAST may be linked to early-onset HSP. The majority of pathogenic mutations were found in the protein\\\'s AAA domain, according to analysis of SPAST sequences; this may be closely related to the pathophysiology of SPG4. The results of this investigation may broaden the range of therapeutic applications for the p.Arg499His mutation in SPAST and offer a chance to investigate the genotype-phenotype relationship of SPG4 in more detail.
Keywords : Spastik Parapleji Tip 4, SPAST Geni, Missense Mutasyon