Novel SOX2 partner-factor domain mutation in a four-generation family

Abstract

Anophthalmia (no eye), microphthalmia (small eye) and associated ocular developmental anomalies cause significant visual handicap. In most cases the underlying genetic cause is unknown, but mutations in some genes, such as SOX2, cause ocular developmental defects, particularly anophthalmia, in a subset of patients. Here, we describe a four-generation family with a p.Asp123Gly mutation in the highly conserved partner-factor interaction region of the SOX2 protein, which is important for cell-specific actions of SOX2. The proband in this family has bilateral anophthalmia and several other family members have milder ocular phenotypes, including typical optic fissure coloboma. Expression studies indicate that Sox2 is expressed in the eye at the site of closure of the optic fissure during development. The SOX2 mutation in this family implicates the partner-factor interaction region of SOX2 in contributing to the specificity of SOX2 action in optic fissure closure. Our findings indicate that investigation of SOX2 in a broad range of eye anomaly patients aids in the determination of particular functions of SOX2 in development.

A Novel Mutation in SOX2 Causes Hypogonadotropic Hypogonadism with Mild Ocular Malformation

“…Recently, Mihelec et al [15] reported a 4-generation family with marked ocular phenotypic variability harboring a D123G SOX2 mutation. These multigenerational patients suggested that there had been no fertility problems in the carriers of the D123G SOX2 mutation.…”

Exome sequencing in developmental eye disease leads to identification of causal variants in GJA8, CRYGC, PAX6 and CYP1B1

“…12 In patients with microphthalmia and anophthalmia, attempts have been made to stratify patients on the basis of the presence of associated eye malformations; however, the overlap in phenotypic features makes this difficult (Figure 1). 13,14 In this study, we applied exome capture and sequencing in patients with developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, and analysed the 56 genes currently known to be implicated in developmental eye disease (Supplementary Table S1). …”

Microphthalmia, late onset keratitis, and iris coloboma/aniridia in a family with a novelPAX6mutation

“…[1][2][3] Genetic defects have been rarely reported in families with autosomal dominant micropthalmia across at least two generations, except for a few families with mutations in OTX2 4 or SOX2. 5 Autosomal dominant keratitis without aniridia has been reported in two families, 6,7 and the disease in one family is associated with a PAX6 mutation. 7 However, we are unaware of previously reported cases of autosomal dominant microphthalmia with late-onset keratitis and iris coloboma/aniridia.…”