PURPOSE: To identify the genetic defect associated with keratoconus (KC) in an Ashkenazi Jewish family and to evaluate its nature and its phenotypic expression within carriers. METHODS: A three generation Ashkenazi Jewish family with KC was ascertained. Diagnosis was based on clinical examination and corneal topography. Segregation analysis was performed using micro-satellite polymorphic markers in close proximity to 7 previously associated KC loci and genes. Mutation analysis of the VSX1 gene was performed by direct sequencing of PCR-amplified exons, and a BseR1 restriction assay. In selected cases, where the genotype was consistent with KC, additional effort to detect subtle corneal changes was made by computerized Orbscan measurements. RESULTS: We found co-segregation between the KC phenotype and a polymorphic marker close to the VSX1. Sequencing revealed a previously described missense mutation (D144E). All of the mutation carriers manifested pathologic corneal findings; some had overt KC while others had subtle corneal alterations identifiable only by Orbscan. CONCLUSIONS: These findings support the pathogenic role of VSX1 gene in KC. The variable expression among the carriers, suggests the involvement of other factors in determining the final phenotype.
PURPOSE: To identify the genetic defect associated with keratoconus (KC) in an Ashkenazi Jewish family and to evaluate its nature and its phenotypic expression within carriers. METHODS: A three generation Ashkenazi Jewish family with KC was ascertained. Diagnosis was based on clinical examination and corneal topography. Segregation analysis was performed using micro-satellite polymorphic markers in close proximity to 7 previously associated KC loci and genes. Mutation analysis of the VSX1 gene was performed by direct sequencing of PCR-amplified exons, and a BseR1 restriction assay. In selected cases, where the genotype was consistent with KC, additional effort to detect subtle corneal changes was made by computerized Orbscan measurements. RESULTS: We found co-segregation between the KC phenotype and a polymorphic marker close to the VSX1. Sequencing revealed a previously described missense mutation (D144E). All of the mutation carriers manifested pathologic corneal findings; some had overt KC while others had subtle corneal alterations identifiable only by Orbscan. CONCLUSIONS: These findings support the pathogenic role of VSX1 gene in KC. The variable expression among the carriers, suggests the involvement of other factors in determining the final phenotype.
Authors: Kathryn P Burdon; Stuart Macgregor; Yelena Bykhovskaya; Sharhbanou Javadiyan; Xiaohui Li; Kate J Laurie; Dorota Muszynska; Richard Lindsay; Judith Lechner; Talin Haritunians; Anjali K Henders; Durga Dash; David Siscovick; Seema Anand; Anthony Aldave; Douglas J Coster; Loretta Szczotka-Flynn; Richard A Mills; Sudha K Iyengar; Kent D Taylor; Tony Phillips; Grant W Montgomery; Jerome I Rotter; Alex W Hewitt; Shiwani Sharma; Yaron S Rabinowitz; Colin Willoughby; Jamie E Craig Journal: Invest Ophthalmol Vis Sci Date: 2011-10-31 Impact factor: 4.799
Authors: Khaled K Abu-Amero; Ali M Hellani; Sameer M Al Mansouri; Hatem Kalantan; Abdulrahman M Al-Muammar Journal: Mol Vis Date: 2011-03-30 Impact factor: 2.367
Authors: Andrea L Vincent; Charlotte Jordan; Leo Sheck; Rachel Niederer; Dipika V Patel; Charles N J McGhee Journal: Mol Vis Date: 2013-04-11 Impact factor: 2.367