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.