Genes of Interest
B3GALTL: Recessive mutations in this glucosyltransferase result in Peters plus syndrome, typically associated with Peters anomaly, short stature, and short hands/limbs, along with other systemic anomalies.
BMP4: Heterozygous disruption of BMP4, an important signaling molecule, by deletion/mutation causes variable ocular (anophthalmia/microphthalmia or anterior segment dysgenesis), digital (polydactyly or syndactyly), brain anomalies, and poor growth. Recently, deletion of BMP4 was linked with SHORT syndrome.
CYP1B1: This cytochrome P450 gene is involved in autosomal recessive congenital glaucoma; occasional cases of anterior segment dysgenesis along with congenital glaucoma have been reported.
FOXC1: Heterozygous deletions/mutations in this transcription factor are seen in Axenfeld-Rieger syndrome with isolated ocular features or ocular, hearing, and heart defects.
FOXE3: A forkhead box transcription factor, dominant mutations result in anterior segment dysgenesis and cataract while recessive mutations cause microphthalmia with sclerocornea.
OTX2: Heterozygous deletion/mutation of OTX2 also results in anophthalmia/microphthalmia or coloboma, sometimes accompanied by systemic anomalies including pituitary defects in particular.
PITX2: Heterozygous deletions/mutations in this homeodomain transcription factor are typically associated with Axenfeld-Rieger syndrome with ocular (anterior segment dysgenesis), dental (small or missing teeth), and umbilical anomalies (umbilical hernia, redundant periumbilical skin).
PITX3: Another homeodomain transcription factor, heterozygous mutations in this gene have been reported in anterior segment dysgenesis and congenital cataract. A homozygous mutation was reported in one patient with microphthalmia and sclerocornea.
SOX2: Heterozygous deletion/mutation of SOX2 results in anophthalmia/microphthalmia, often in combination with systemic anomalies including brain, pituitary, gastrointestinal, poor growth, genitourinary, and muscle anomalies. Mutations in SOX2 explain 15-20% of anophthalmia/microphthalmia.
VSX2 (CHX10): Homozygous mutations in this homeodomain containing transcription factor results in isolated microphthalmia with or without coloboma and other ocular defects.
In addition to study of known genes associated with ocular conditions, we are actively working to identify new genetic factors which contribute to human ocular disorders. Candidate genes are identified through animal studies, array-based comparative genomic hybridization (array-CGH) to detect small areas of deletion/duplication, and whole exome/genome sequencing to identify mutations in novel factors.