Karaman, S. S.; Sevik, T.; Akdemir, S.; Bilgin, B.; Karadeli, E.; Yalcin, D.; Baran, B.; Gelsin, B.; Budaklar, B.; Sert, B.; Gulden, G.; Tastan, C.

Wu Syndrome, also known as X-Linked Wu Type Intellectual Developmental Disorder, is caused by a mutation in the GRIA3 (Glutamate Ionotropic Receptor AMPA Type Subunit 3) gene located at position 25 on the X chromosome. GRIA3 encodes iGluR3, a subunit of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor, which plays a critical role in rapid excitatory synaptic transmission in the central nervous system. This receptor is essential for learning, memory, and the processes of long-term depression (LTD) and long-term potentiation (LTP). Despite its significance, Wu Syndrome remains under-researched and lacks effective treatments. Some genetic variants have been identified, but many, including the W637S variant, are still unstudied. This study pioneers the development of a Wu Syndrome model in neural cell lines using genetic modification techniques to identify and characterize new GRIA3 variants. By focusing on variants such as G833R and W637S, this research provides novel insights into their effects on GRIA3 function, paving the way for potential therapeutic strategies. This is the first study to explore the responses of neural cells to these mutations in vitro, thereby contributing valuable knowledge toward understanding and treating Wu Syndrome.