Abstract
Purpose :
Inherited retinal disorders (IRD) are challenging to diagnose because of genetic heterogeneity and overlapping phenotypes. Genetic testing helps determine the underlying molecular pathophysiology, confirms the clinical diagnosis, estimates the risk of recurrence, and determines possible eligibility for future gene-based therapies. We report a case of a patient with two previously unreported mutations in KCNV2, a gene strongly linked to CDSRR.
Methods :
Ocular assessment was done, which included visual acuity assessment, slitlamp, and dilated fundus examination. Magnetic resonance imaging, full-field electroretinography (ffERG), and optical coherence tomography were done. Whole blood was obtained, DNA extracted, and genetic testing was performed through the My Retina Tracker Program of Blueprint Genetics, which screened 285 genes for disease-causing mutations implicated in IRDs.
Results :
An 8-year old Chamorro female presented with congenital nystagmus, high myopia progression, and preferential right gaze since infancy. Medical and family histories were unremarkable. Ocular exam showed BCVA of 20/200, myopic fundus, and thin macula in both eyes. ffERG was consistent with cone dystrophy. Neurologic workup was unremarkable. The IRD gene panel test showed the patient was compound heterozygous for two nonsense mutations in KCNV2: c.153T>A, p.(Tyr51*) and c.625G>T, p.(Glu209*). Tyr51* is absent in the Genome Aggregation Database control population cohort while one individual is heterozygous for Glu209*.
Conclusions :
To our knowledge, this study is the first to identify these two nonsense mutations in KCNV2 in a patient with CDSRR. Both mutations are predicted to lead to loss of normal protein function either through protein truncation or nonsense mediated decay. KCNV2 encodes the voltage-gated potassium channel subunit Kv8.2. Deficiency of Kv8.2 can influence the photoreceptor membrane potential and is thought to cause the visual symptoms of patients. Identifying these novel mutations highlights the value of genetic testing, especially in underrepresented minorities such as Asia Pacific Islanders, as these guided the clinical management and anticipation of disease progression.
This is a 2021 ARVO Annual Meeting abstract.