Zoe Hill

Helios Scholar

Okur-Chung neurodevelopmental syndrome (OCNDS) (OMIM# 617062) is an autosomal dominant disorder caused by heterozygous mutations in the CSNK2A1 gene localized on chromosome 20p13.1. The c.593A>G (p.Lys198Arg)  is the most frequently occurring mutation within the CSNK2A1 gene that causes OCNDS. CSNK2A1 gene encodes for the alpha subunit of Casein kinase II (CK2), a serine/threonine protein kinase involved in various cellular processes. CK2 also plays an essential role in regulating mitochondrial homeostasis, and it has been demonstrated that CK2 regulates protein import into mitochondria through the translocase of the outer membrane (TOM complex) proteins. In this study, we aimed to elucidate mitochondrial dysfunction in OCNDS patient-derived fibroblast cell lines with p.Lys198Arg mutation. We utilized techniques such as RNA sequencing, confocal imaging, and western blot analysis to achieve this. The OCNDS cell lines exhibited several distinct characteristics, such as reduced mitochondrial membrane potential, observable morphological changes, and alterations in protein phosphorylation patterns. These initial observations robustly point to mitochondrial dysfunction in cellular models of OCNDS syndrome. Subsequent research efforts will be directed toward understanding the precise molecular underpinnings of this dysfunction and investigating potential therapeutic avenues to restore mitochondrial dysfunction in OCNDS patients.