Akademik Veri Yönetim Sistemi
HIBIT2024 (17th International HIBIT Conference), İstanbul, Türkiye, 18 - 20 Aralık 2024, ss.156, (Özet Bildiri)
SYNGAP1 is a synaptic Ras GTPase-activating protein that is very important during neurodevelopmental processes. It participates in synaptic plasticity and motor coordination. Recently, variants in this gene were implicated in neurodevelopmental disorders and some authors suggested its possible contribution to the occurrence of cerebral palsy. This study investigated a patient diagnosed with CP through whole-exome sequencing, identifying the L284R mutation in the SYNGAP1 gene. Our analyses classified this variant as pathogenic. To evaluate its molecular consequences, we utilized in silico tools including PyMOL, FoldX, and I-Mutant. The L284R mutation, which substitutes a nonpolar leucine with a positively charged arginine, demonstrated destabilizing eÉects on protein structure with a calculated ΔΔG of -1.81 kcal/mol. The mutation also altered the epitope structure (KRYYCELCLDDMLYA), potentially disrupting interactions necessary for motor function. Additionally, narrowing of the tunnel within the C2 domain (from 1.6 Å to 1.2 Å) was observed, potentially aÉecting ligand binding and synaptic stability. These findings suggest that the L284R mutation may contribute to synaptic and motor dysfunction. Further studies are necessary to confirm its association with CP and to explore therapeutic strategies.