The SIX gene family consists of six members (SIX1–SIX6), which all contain two shared protein domains; a DNA binding homeobox domain and a SIX domain, which binds downstream effector molecules. These genes are conserved and were originally identified through homology to the Drosophila melanogaster (Drosophila) Sine Oculis (SO) gene, which is required for proper eye development. SIX6 is closely related toSIX3 and is expressed in the developing and adult human retina. It is also expressed in the hypothalamic and the pituitary regions.
Defects in this gene are the cause of optic disk anomalies with retinal and/or macular dystrophy, characterized by optic nerve dysplasia, optic disk anomalies, chorioretinal dystrophy and macular atrophy.
The SIX6 gene spans 3.9kb of genomic DNA and is split in two exons that are translated into a 246 amino acids. Chromosomal mapping of SIX6 revealed that it is closely linked to SIX1 and SIX4 in human chromosome 14q22.3–q23. Mutations within this gene have been identified in patients with optic disk anomalies with retinal and/or macular dystrophy.
See: [Syria>Aldahmesh et al. (2013)]
Aldahmesh et al. (2013) described two brothers with microphthalmia associated with anterior and posterior segment dysgenesis, born to first cousins Syrian parents. Using genotyping and autozygome analysis, a homozygous frame-shift deletion c.532_536del in SIX6 gene was found in both children, and it was heterozygous in the parents. This mutation was absent in 200 Saudi normal controls and in the 1000 genomes project.