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E Heon, KK Kopp, R Bremner, D Rootman, RL Chow, K Dorval, AL Vincent, C Westall, JE Sutphin, EM Stone; VSX1: A gene for Posterior Polymorphous Dystrophy and Keratoconus . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2871.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:Provide molecular characterization of posterior polymorphous dystrophy (PPD) and keratoconus (KC). Methods:VSX1 was selected as a candidate gene its coding sequence was screened for mutations by a combination of SSCP and direct sequencing. The population studied included 22 patients with PPD, 63 patients with KC, 90 patients with Fuch's corneal dystrophy and 90 patients with open angle glaucoma. Results:We identified mutations in the VSX1 homeobox gene for two distinct inherited corneal dystrophies; PPD and KC. One mutation (R166W) was responsible for KC, altered the homeodomain and impaired DNA-binding. Two other sequence changes (L159M and G160D) were associated with KC and PPD respectively and involved a region adjacent to the homeodomain. The G160D substitution, and a fourth defect affecting the highly conserved CVC domain (P247R), occurred in a child with very severe PPD who required a corneal transplant at 3 months of age. In this family, relatives with the G160D change alone had mild to moderate PPD, while P247R alone caused no corneal abnormalities. However, with either the G160D or P247R mutation, electroretinography detected abnormal function of the inner retina, where VSX1 is expressed. Conclusion:These data define the molecular basis of two important corneal dystrophies and reveal the importance of the CVC domain in the human retina.
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