The HMG-box transcription factor Sox2 plays a role throughout neurogenesis and also acts at other stages of development, as illustrated by the multiple organs affected in the anophthalmia syndrome caused by SOX2 mutations.
This case confirms that haploinsufficiency for SOX2 plays a crucial role in human eye development and emphasizes the necessity of careful chromosomal analysis, including FISH analysis of the 3q region, in case of prenatal discovery of anophthalmia.
No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia.
We show that Rbm24-targeted deletion using a constitutive CMV-driven Cre in mouse, and rbm24a-CRISPR/Cas9-targeted mutation or morpholino-knockdown in zebrafish, results in Sox2 down-regulation and causes the developmental defects anophthalmia or microphthalmia, similar to human SOX2-deficiency defects.