Decoding Genomic Variants in a Turkish Cohort of Patients with Spasticity

Hereditary spastic paraplegia (HSP) is a complex neurological disorder with significant genetic heterogeneity. Overlapping clinical presentations and population-specific genetic variants pose challenges to differential diagnosis and genetic studies. To identify and characterize genetic variants associated with HSP and related syndromes in a Turkish cohort, emphasizing potential novel findings and inheritance patterns. 45 patients were clinically diagnosed with HSP or related phenotypes and their demographic and clinical details were recorded. Clinical exome sequencing (CES) was employed to identify pathogenic and likely pathogenic variants. Variants were classified using ACMG guidelines and critical variants were confirmed by Sanger sequencing. The cohort included 16 females (35.5%) and 29 males (64.5%), aged 3 months to 72 years. Consanguinity was identified in 70.4% of cases with reported parental data. Pathogenic or likely pathogenic variants were detected in 66.7% of patients. Commonly affected genes included SPAST (17.8%), SPG7 (13.3%), and SPG11 (11.1%). Fifteen novel variants were identified, expanding the known genetic spectrum of HSP. This study highlights the clinical utility of CES in diagnosing HSP and related disorders, identifies novel genetic variants, and provides evidence for complex inheritance mechanisms. These findings enhance the understanding of the genetic landscape of HSP, particularly in the Turkish population.