Functional analysis of a novel segment deletion in the FRMD7 gene causing X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus (ICN) is characterized by involuntary horizontal eye oscillations and is frequently associated with X-linked FRMD7 mutations. Despite over 150 FRMD7 variants have been reported, their pathogenic mechanisms remain poorly understood. In this study, we identified a novel FRMD7 deletion (c.742-211_1050+59del p.Leu249_Val351del) in an ICN-affected family. Minigenes analysis demonstrated that this FRMD7 mutation caused skipping of exon 9- 11. RT-qPCR and western blotting revealed unchanged FRMD7 mRNA levels but a significantly upregulated in protein expression. Structural modeling indicated the loss of a crucial amino acid segment in the mutated FRMD7 protein (FRMD7-m1). These findings suggest that this FRMD7 deletion disrupts protein translation and stability, contributing to ICN pathogenesis, and expand our understanding of FRMD7-related molecular mechanisms.