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

Developmental eye diseases, including cataract/microcornea, Peters anomaly and coloboma/microphthalmia/anophthalmia, are caused by mutations encoding many different signalling and structural proteins in the developing eye. All modes of Mendelian inheritance occur and many are sporadic cases, so provision of accurate recurrence risk information for families and affected individuals is highly challenging. Extreme genetic heterogeneity renders testing for all known disease genes clinically unavailable with traditional methods.

Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia/microphthalmia in offspring.

Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities.

Twist2: role in corneal stromal keratocyte proliferation and corneal thickness.

Purpose: Twist2 is a member of a family of bHLH transcription factors critical for normal mesenchymal proliferation and differentiation. In this study, the authors analyzed the role of Twist2 in the eye and cornea through examination of a Twist2 loss-of-function mouse mutant.

Methods: Twist2 expression during eye development in the mouse was investigated using RT-PCR and mRNA slide in situ hybridization.

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

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.