Journal of Clinical and Experimental Ophthalmology
Open Access

Abstract

A novel NYX gene mutation identified in a Chinese Northeast Han family with high myopia and night blindness

Xiaoyi*

Objective: This study aimed to investigate and identify the underlying pathogenic gene mutation responsible for high myopia and congenital night blindness within a family from Northeast China, thereby contributing to a better understanding of the genetic basis and hereditary patterns associated with these ocular disorders.

Methods: Whole-exome sequencing was conducted to screen for genetic variations among family members, while AlphaFold2 was utilized to predict the tertiary structure of the associated protein. This structural analysis was further complemented by molecular dynamics simulations to assess conformational alterations resulting from the identified mutation. In parallel, comprehensive clinical evaluations, including detailed ophthalmic examinations, assessment of refractive status, and fundus imaging, were performed to characterize the phenotypic manifestations and correlate them with the genetic findings.

Results: A novel frame shift mutation, c.264dup (p.R89Afs*26), was identified in exon 3 of the NYX gene, leading to premature truncation of the C-terminal functional domain. The proband presented with extremely high myopia (spherical equivalent<-23.00D) accompanied by classic symptoms of congenital night blindness. Structural analysis revealed pronounced conformational changes in the mutated protein, notably disrupting the interaction interface with mGluR6. Pedigree analysis further supported an X-linked recessive inheritance pattern, aligning with the clinical and genetic findings within the affected family.

Conclusion: This study is the first to report that the NYX c.264dup mutation leads to complete congenital stationary night blindness accompanied by extreme high myopia, thereby expanding the known mutation spectrum of the NYX gene. These findings offer valuable insights for improving molecular diagnosis and facilitating genetic counseling for affected individuals and families, while also providing new perspectives on the molecular mechanisms linking retinal signal transduction to pathological axial elongation.

Published Date: 2025-08-24; Received Date: 2025-07-16