The COL18A1 gene encodes the alpha chain of type XVIII collagen. There are three isoforms of the alpha 1 subunit of collagen XVIII, which form three different lengths of the collagen XVIII protein. The short isoform of collagen XVIII is found in basement membranes throughout the body, including several parts of the eye. The two longer isoforms are found primarily in the liver. The function of collagen XVIII is not well known, but it appears that all of the isoforms are involved in determining the retinal structure as well as in the proper closure of the neural tube. Endostatin, which is produced by proteolytic processing at several endogenous cleavage sites in the C-terminal domain, inhibits endothelial cell proliferation and angiogenesis. Defects in this protein are the cause of Knobloch syndrome, an autosomal recessive disorder characterized by vitreoretinal and macular degeneration and occipital encephalocele.
Aldahmesh et al., (2011) described 13 patients from six consanguineous Saudi families with Knobloch syndrome. All affected patients except one (patient 6), had truncated homozygous mutations in COL18A1 gene. Patient 6, who did not have a mutation in the COL18A1 gene, was a 7-year-old girl presented with progressive retinal degeneration and serous retinal detachment. Using autozygosity mapping exome sequencing for patient 6, a novel homozygous missense mutation c.536C>T (p.Ser179Leu) was identified. Her both parents were heterozygous for this mutation, while her healthy siblings were homozygous for the wild-type allele. This mutation was not found in 386 Saudi control samples or in the Exome Variant Server.
Khan et al., (2012) described four consanguineous Saudi families with a total of seven children (aged between 4-15 years) affected with Knobloch syndrome. All four families were found to have a separate homozygous mutation in the COL18A1 gene. These four mutations were c.355delG (p.V119SfsX5), c.2743C>T (p.R915X), c.3514_3515delCT (p.L1172VfsX72), and c.1785_1786delinsA (p.P597LfsX127).