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W. Ferrini, C. Willoughby, N. Noordeh, G. Billingsley, S. Kaye, E. Héon; Genetic heterogeneity of familial Keratoconus and Posterior polymorphous dystrophy. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2884.
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Purpose: The incidence of keratoconus (OMIM#148300) is estimated to be 1 in 2000 of the population. It is the leading cause of corneal transplantation in the Western world. This condition is in part genetically determined and genetically heterogeneous. Several studies suggest that familial keratoconus has an autosomal dominant inheritance with incomplete penetrance and variable expression. Its clinical spectrum is great and can overlap with posterior polymorphous dystrophy (PPD). Mutations in VSX1 (OMIM#605020), the only keratoconus gene identified to date, account for only a fraction of these cases. Additional candidate loci on chromosomes 1 (COL8A2), 15 and 16 were recently reported. The purpose of this study was to map the disease causing–gene in a three generation family affected with keratoconus and posterior polymorphous dystrophy. Methods: Eleven Caucasian family members (5 affected and 6 unaffected) of a four generation family from the UK affected with PPD and keratoconus were studied. All participants had a full ocular assessment including corneal topography and pachymetry. Diagnosis of PPD in the proband was histologically proven by light microscopy and immunohistochemistry after therapeutic keratoplasty. Haplotype analysis was done using microsatellite markers covering the four candidate loci: VSX1, COL8A2 and the two other candidate regions on chromosomes 15 (D15S153 to D15S653) and 16 (D16S2624 to D16S3138). Results: VSX1, COL8A2 and the candidate loci on chromosomes 15 and 16 were excluded by haplotype analysis in this family. Conclusion: The genetic analysis of this family suggest the existence of an additional Keratoconus/PPD locus, yet to be identified.
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