Genetic phenotypic characteristics and inheritance patterns of patients with achromatopsia at a large academic institution and a review of the literature and gene therapies

Purpose Achromatopsia (ACHM) is a cone dysfunction syndrome associated with low color vision, photophobia, and congenital nystagmus. Pathogenic variants in the CNGA3 and CNGB3 genes are the most common causes of ACHM. Identifying the underlying genetic etiology in patients with clinical findings of ACHM is critical to establishing the diagnosis and selecting targets for gene therapies. This study utilizes the inherited retinal disease (IRD) database at the University of Minnesota (UMN) to understand clinical features of achromatopsia, potential diagnostic methods, and genetic variability at one large academic institution. Methods This retrospective cohort study examined patients with a genetically confirmed diagnosis of ACHM evaluated at the UMN/M Health IRD clinic between May 2015 and August 2022. Data were collected through UMN’s electronic health record system and included information on demographics, history of ocular illness, visual acuity, and diagnostic exam results, such as electroretinogram, fundus autofluorescence, and optical coherence tomography (OCT) imaging. Genetic testing was performed using next-generation sequencing panels of varying sizes, and variants were interpreted according to American College of Medical Genetics guidelines. Results A total of 21 patients with a genetically confirmed ACHM were included in the study. Most patients were female (67%) and white (76%). The cohort included one pair of twin siblings and one group of three siblings. The median age of genetic testing conducted was 12 years (interquartile range, 12-20 years). One-third of patients had nyctalopia. All patients experienced difficulties with color vision, 20 of 21 (95.2%) had photosensitivity, and 18 of 21 patients reported congenital nystagmus. Diagnostic imaging showed most patients with a normal scotopic response and absent photopic response on electroretinogram, macular hyperfluorescence on fundus autofluorescence, and normal optical coherence tomography imaging. Conclusion This study contributes to an understanding of the phenotypes and distribution of genetic variants associated with achromatopsia at a single academic institution in the state of Minnesota, particularly those involving the CNGA3 and CNGB3 genes. Future research could explore the prevalence of these variants in larger cohorts to enhance clinical management and treatment strategies for patients with achromatopsia.