Corresponding Author: 
Gholson J. Lyon
Email: gholsonjlyon@gmail.com
ABSTRACT
Copy number variations (CNVs), among other genetic abnormalities, have been implicated in a range of disorders and can result in a variety of clinical manifestations, such as intellectual disability, developmental disorders, and cancer. The role of specific genes within such CNVs, especially novel or rare genes, is the subject of ever-advancing contemporary genetics research. The identification and characterization of these genes play an important role in understanding the pathophysiology of many different medical conditions and shed light on diagnosis refinement and different strategies for treatment. This case study looks at the genetics underlying the clinical presentation in a patient exhibiting epilepsy, spinal abnormalities, and intellectual disability, with a focus on identifying the underlying genetic basis for this presentation. Here we show a novel de novo 2.62 Mb interstitial deletion at 6q22.1_q22.31 implicates the NUS1 gene as a significant contributor to the observed phenotypes. NUS1 classically has been associated with congenital disorders of glycosylation and intellectual disability. However, our findings regarding this deletion suggest a broader phenotypic spectrum for NUS1 variants, encompassing manifestations like kyphosis, choreoathetosis, and possible dyskinesias, which were not notably linked to this gene before. This paints a clearer picture of NUS1 ’s clinical relevance beyond previously known links. The results of this report also add to the building body of evidence that highlights the significance of CNVs in neurological and developmental disorders. Our findings reinforce the importance of genetic analysis in patients presenting with atypical symptoms.