Abstract
Abstract: :
Purpose: To characterize the population of patients with various anterior segment anomalies for mutations in PITX2, PITX3, FOXE3 and VSX1 genes that were previously shown to be involved in related ocular disorders. Methods: A total of 220 samples from patients with anterior segment anomalies, isolated or associated with other congenital abnormalities, was collected. The DNA samples were examined by PCR amplification of the gene regions and further analysis of the obtained PCR products on SSCV-gel and/or by direct sequencing for variants in the gene sequence. The complete coding sequence of each gene and also sequences of some likely regulatory elements were included in the screening. Results: Mutations in PITX2 gene were found to be involved in approximately 35% of Rieger syndrome patients and 5% of patients with isolated ocular anomalies. Most of the PITX2 mutations were found in the homeobox region of the gene that encodes the DNA-binding domain. Mutations in PITX3 gene were found to affect about 10% of patients with cataracts and ASMD in our sample. In contract with the PITX2 gene, PITX3 mutations are located in regions that encode the N- and C-terminal regions of the gene and not the homeodomain. Most of the PITX2 and PITX3 gene mutations are unique mutations with several hotspots identified in both genes. Several novel variants were identified in the VSX1 gene and their possible involvement in anterior segment disorders is currently under study. Analysis of affected families for possible multiple gene involvement in the development of disease using sequence variants identified in all three genes, failed to identify any such families. Direct sequencing analysis of the FOXE3 gene is currently in progress. Conclusion: The PITX2, PITX3, FOXE3 and VSX1 genes play important role in ocular development. Mutations of PITX2 gene are most commonly associated with Rieger syndrome while mutations in PITX3 gene- with ASMD/cataract phenotype. More studies of VSX1 and FOXE3 genes need to be performed to identify a spectrum of phenotypes caused by mutations in these genes. Anterior segment disorders are highly heterogeneous.
Keywords: 420 genetics • 507 pathology: human • 318 anterior segment