Disease relevance of SIX6

• Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies [1].
• PURPOSE: To investigate whether 173 patients with microphthalmia, anophthalmia, and coloboma have mutations in the eye-development gene SIX6 [2].

High impact information on SIX6

• Gain-of-function studies in medaka show a clear synergistic activity between SIX3/SIX6 and TLE1, which, on its own, can expand the eye field [3].
• Tle1 and Aes are expressed in the developing eye of medaka fish (Oryzias latipes) embryos, overlapping with the distribution of both Six3 and Six6 [3].
• Absence of SIX6 mutations in microphthalmia, anophthalmia, and coloboma [2].
• METHODS: The two exons of the SIX6 gene were amplified by PCR from patients' genomic DNA and directly sequenced to search for mutations [2].
• Optx2 had some inhibitory effects on photoreceptor differentiation, which were accompanied by marked increases in the frequency of morphologically undifferentiated cells [4].

Biological context of SIX6

• SIX6 spans 2567 bp of genomic DNA and is split in two exons that are transcribed into a 1393-nucleotide-long mRNA [1].
• Chromosomal mapping of SIX6 revealed that it is closely linked to SIX1 and SIX4 in human chromosome 14q22.3-q23, which provides clues about the origin and evolution of the vertebrate SIX family [1].
• Mutations in three of these genes in man (SIX5, SIX6 and SIX3) are associated with severe phenotypes, and therefore, the cloning of other human genes from this family is of interest [5].
• Analysis of the developmental SIX6 homeobox gene in patients with anophthalmia/microphthalmia [6].

Anatomical context of SIX6

• Six9 (Optx2) is first expressed at presomitic stages in the head-fold, both in the neural plate and in the underlying axial mesoderm [7].

Other interactions of SIX6

• Exclusion of SIX6 hemizygosity in a child with anophthalmia, panhypopituitarism and renal failure [8].
• Recently it has been suggested that the human homeobox gene, SIX6, and the BMP-4 gene are responsible for eye development [9].

Analytical, diagnostic and therapeutic context of SIX6

• The patient reported here had a normal karyotype and Southern blot did not reveal loss of one copy of SIX6 [8].

References