Novel SOX2 Mutations and Phenotypes

Abstract

Purpose: : Anophthalmia and severe microphthalmia are debilitating ocular conditions with associated ocular anomalies including sclerocornea, cataract and ocular coloboma. The underlying disease genes and causes for variability in expression of associated ocular features are poorly understood. Heterozygous SOX2 mutations are found in approximately 10% of patients with anophthalmia and severe microphthalmia, and less frequently mutations are found in other genes including OTX2, RAX, PAX6, CHX10, STRA6 and BMP4. In this project we have investigated Australian patients with anophthalmia/microphthalmia and other developmental ocular anomalies for the presence of SOX2 mutations.

Methods: : Detailed clinical investigation of phenotypic features in patients with microphthalmia and/or associated developmental ocular anomalies. Sequencing of the coding exon and surrounding sequences of SOX2 in these patients. Sox2 expression analysis in the developing murine eye.

Results: : Novel SOX2 mutations and associated phenotypic features are identified in our patient cohort. Sox2 expression analysis indicates correlation between likely mutation impact and clinical ocular phenotypes.

Conclusions: : Recognition of additional phenotypic features that may be associated with SOX2 mutations is important to prompt investigation of this gene in similarly affected patients. Correlation of the phenotypes with the gene regions affected by the mutations can shed light on likely specific functions of SOX2 in eye development.

Keywords: genetics • development