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G Silvestri, DP Dash, DG Frazer, AJ Jackson, AE Hughes; Linkage Analysis in a Large Family With Cataract and Keratoconus . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3228.
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Purpose: Keratoconus is a bilateral but asymmetrical corneal dystrophy which results in significant visual morbidity in young adults. Keratoconus usually occurs sporadically however approximately 10% of cases are inherited. We have identified a 3 generation Irish family with early developmental cataract and keratoconus which are inherited in an autosomal dominant manner. The purpose of this study is to document the clinical phenotype and to identify linkage in this pedigree. Methods: 46 members of the family were examined, 17 affected and 29 unaffected. Visual function and refractive status were ascertained. The clinical features were documented using conventional slitlamp biomicroscopy, keratometry and corneal topography . Venous blood was taken for DNA analysis. The family were examined on 2 occasions, 4 years apart in order to determine age of onset of both cataract and keratoconus. A candidate gene approach to known cataract loci was initially undertaken. Linkage was not identified. A full genome-wide search is currently underway with 75% of the genome having been excluded. Results:Clinical observation shows that the onset of cataract in the 3rd generation is in late childhood, usually around the age of 8-10 years. This is usually preceded by the onset of progressive astigmatism with keratoconus becoming clinically manifest in the early teens. Detailed examination of the age of onset in the 3 generations indicates that the disease may be showing anticipation. Conclusion:We present a 3 generation family with autosomal dominant keratoconus and developmental cataract. Linkage analysis to known cataract loci is negative. We are proceeding with a genome search to determine linkage. It is expected that this family will lead to the first definitive locus for keratoconus.
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