SOX2 mutation causes anophthalmia, hearing loss, and brain anomalies.

The SOX2 transcription factor is expressed early in the embryonic stem cells of the blastocyst and later in the neural stem cells. It is a member of the SOX family of proteins that carry a DNA-binding high-mobility group domain and additional domains that regulate embryonic development and cell fate determinations. We surveyed 93 patients with severe eye malformations for mutations in SOX2. Here, we report a novel nonsense mutation in one female patient with bilateral clinical anophthalmia, absence of all optic pathways, and other neurological abnormalities. The mutation, Q155X, creates a premature termination codon early in the transcriptional activation domain and is likely to be a null allele. Our data show that mutations in SOX2 can cause not only anophthalmia, but also aplasia of the optic nerve, chiasm and optic tract, as well as modest bilateral sensorineural hearing loss, and global developmental delay, underscoring the importance of SOX2 in early human eye and brain development.