Molecular Analysis of Consanguineous Families Having X-Linked Congenital Stationary Night Blindness in Khyber Pakhtunkhwa, Pakistan

Abstract

X-linked congenital stationary night blindness (XLCSNB) is a vision disorder characterized by reduced visual acuity, myopia (short-sightedness), strabismus, and nystagmus. This condition results from mutations affecting the transmission of visual signals in the retina. Genetic studies have identified the proximal short arm of chromosome X (Xp11.4) as the region harboring the candidate gene associated with XLCSNB. Electroretinogram (ERG), a diagnostic test, plays a critical role in differentiating XLCSNB categories by evaluating the electric responses of retinal, bipolar, and ganglion cells to light and dark stimuli. To locate the candidate gene, four microsatellite markers (DXS574, DXS8012, DXS993, and DXS1201) were designed near the proximity of the target region on Xp11.4. The gene was identified as the NYX gene, encoding nyctalopia, a 481-amino-acid protein, and a member of leucine-rich repeats (LRR). Nyctalopia plays a pivotal role in signal transmission between retinal and bipolar cells. The expression of the NYX gene is low in tissues such as muscles, the brain, the retina, and the testis. Following linkage analysis, specific primers were designed to amplify both exons of the NYX gene. Gel electrophoresis was used to observe DNA bands, and subsequent sequencing of the gene was performed to identify mutations associated with XLCSNB. Three mutations were identified in the NYX gene, all of which had been reported previously. These mutations, predominantly splicing mutations, are known to be pathogenic alterations. The NYX gene encodes 13 leucine-rich repeats (LRRs), and the identified missense mutations primarily affect these LRR sites, leading to impaired retinal signal transmission and disturbed eye function. To date, 42 different mutations in the NYX gene have been reported, with splicing mutations being the most common. This study successfully identified mutations in the NYX gene associated with XLCSNB. Although previously reported, the findings provide further insight into the molecular mechanisms underlying this disorder. Future research should focus on functional analyses of the NYX genes to better understand their role in regulating retinal cell interactions and signaling pathways.