Genetic screening of the RNA-binding protein RBM24 and its binding sites in the SOX2 3’ untranslated region in a cohort of 50 patients with micro-anophthalmia

Microphthalmia and anophthalmia (M/A) are rare congenital eye anomalies with a birth prevalence of up to 1 in 10,000 births. The etiology of M/A can involve environmental and/or genetic factors, with a genetic origin identified in approximately 50% of cases through analysis of key genes. The transcription factor SOX2 is the most commonly implicated gene, accounting for around 15% of M/A cases. Recent studies have shown that the RNA-binding protein Rbm24 post-transcriptionally regulates Sox2 expression in mice and zebrafish, with Rbm24 null models exhibiting eye phenotypes in both species. Rbm24 can bind to Sox2 mRNA via three AU-Rich elements (AREs) located in its 3’ untranslated region (UTR). In this study, we aimed to determine whether pathogenic variants within RBM24 or the SOX2 3’UTR AREs were present in a cohort of 50 individuals with M/A with no identified genetic cause for their condition. Despite the ocular defects observed in animal models, we did not detect any variant of interest in these candidate regions in our cohort. Although we cannot exclude the involvement of pathogenic variations in RBM24 or the SOX2 3’UTR AREs in ocular developmental defects, our study shows that they are unlikely to represent a frequent cause of M/A.