Despite numerous studies associating Visual System Homeobox 1 (VSX1), with posterior polymorphous corneal dystrophy and keratoconus, its role in these diseases is unclear.
In our case-control sample panel and the larger familial sample panel, we did not observe the reported polymorphism of the VSX1 gene, and the distribution of these 3 polymorphisms was not significant enough to support a pathogenetic role in keratoconus.
Mutational analysis of the VSX1 gene in a series of Italian patients revealed one novel mutation and confirmed an important role played by this gene in a significant proportion of patients affected by keratoconus, when it is inherited as an autosomal dominant trait with variable expressivity and incomplete penetrance.
To determine whether patients with sporadic, non-familial keratoconus and no pathogenic mutations in the visual system homeobox 1 (VSX1) gene have evidence of chromosomal copy number alterations.
Molecular analysis identified the VSX1 mutation Q175H in the affected brother and in the mother who had neither VKC nor keratoconus but only the VSX1Q175H sequence change.
Our investigation showed that KTCN-related sequence variants of analyzed genes were found in a very small proportion of the studied patients indicating that genes other than VSX1, TGFBI, DOCK9, IPO5, and STK24 are involved in the development and progression of KTCN in Polish patients.
We did discover a significant association of 627+23G>A polymorphism distribution (VSX1) with unrelated patients diagnosed with the hereditary form of KC.
A total of 66 unrelated patients with keratoconus from the European population (27 with familial keratoconus; 39 with sporadic keratoconus) were analysed for VSX1 mutations.
In our case-control sample panel and the larger familial sample panel, we did not observe the reported polymorphism of the VSX1 gene, and the distribution of these 3 polymorphisms was not significant enough to support a pathogenetic role in keratoconus.
DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN.
The present report focuses on the VSX1 gene, for which there is general agreement that it is involved in KC and other corneal pathologies, and critically details the evidence for its involvement in KC.
Molecular analysis of the five genes in a cohort of 225 sporadic and 77 familial keratoconus cases confirms the possible pathogenic role of VSX1 though in a small number of patients; a possible involvement of LOX and TIMP3 could be excluded; and the role played by SOD1 and SPARC in determining the disease as not been definitively clarified.