SLC35A2 and Intractable Focal Epilepsy: Investigation and Characterization of Underlying Changes in Glycosylation and Neuronal Development using iPSC model of Patient- Derived SLC35A2 Variants

<span style="font-weight: 400;">Focal epilepsy is a common neurological disorder that accounts for an estimated 61 percent of the worldwide prevalence of epilepsy and has high rates of intractability. Sequencing of DNA from leukocytes and resected tissue has identified germline and somatic variants in </span><em><span style="font-weight: 400;">SLC35A2</span></em><span style="font-weight: 400;"> in some congenital disorders of glycosylation and mild malformations of cortical development, respectively. </span><em><span style="font-weight: 400;">SLC35A2 </span></em><span style="font-weight: 400;">codes for the UDP-galactose transporter located within the Golgi apparatus that is crucial for glycosylation and posttranslational modification of proteins, and previous research has indicated that variant cells display altered glycosylation and precocious development.</span> <span style="font-weight: 400;">In this study, I sought to examine the impact of variants in </span><em><span style="font-weight: 400;">SLC35A2</span></em><span style="font-weight: 400;"> on maturation, expression of </span><em><span style="font-weight: 400;">SLC35A2</span></em><span style="font-weight: 400;">, and glycosylation across two induced pluripotent stem cell (iPSC) lines using molecular biology and immunogenetic analysis, as well as replicate and extend prior observations seen in another iPSC cell line. I found that neuronal populations derived from the iPSC line with </span><em><span style="font-weight: 400;">SLC35A2</span></em><span style="font-weight: 400;"> variants show altered </span><em><span style="font-weight: 400;">N</span></em><span style="font-weight: 400;">-glycosylation, longer average neurite length, and earlier presentation of development markers, indicating a role of </span><em><span style="font-weight: 400;">SLC35A2</span></em><span style="font-weight: 400;"> in brain development and demonstrating these roles in multiple independent iPSC lines.&nbsp;</span>