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L. Richter, J.L. Turner, P. Flodman, F.R. Barría von-Bischhoffshausen, M.A. Spence, J.B. Bateman; Screening of an Autosomal Dominant Cataract Family (ADC 53) for Known ADC Loci . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1262.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To map and identify the gene for ADC in a large Chilean family. Methods: ADC 53 is a four generation Chilean family consisting of 41 individuals with 17 affected individuals. Clinically, affected individuals had cataracts with features varying from posterior subcapsular and pulverulent opacities in the embryonal and cortical regions. SIMLINK analysis was used to estimate the power to detect linkage in a subset of 28 members of ADC 53. We screened the subset of the family with a panel of markers for known ADC loci using PCR amplifications performed separately for each primer set. The products were resolved on an ABI 373 using Genescan 2.1 software (Applied Biosystems). Two point LOD scores were calculated using LIPED. Results: For a tightly linked marker, we estimated that linkage analysis in the chosen subset of this family will have 70% power to detect a LOD greater than 3; the maximum LOD score achieved over 1000 simulations was 5.62. We calculated LOD scores between the ADC 53 locus and markers on chromosomes 1, 2, 10, 11, 12, 15, 16, 17, 19, 20, 21, and 22 and excluded all except for chromosome 22 based on lack of evidence of linkage or co-segregation. Markers on chromosome 22 yielded the highest LOD score of 3.59 for D22S258. Conclusions: Using our ADC screening panel, we excluded linkage in this family with markers know to be linked to human ADC except those on chromosome 22. We have demonstrated linkage of the locus in the ADC 53 family to chromosome 22q. This region contains a cluster of ß crystallin genes; CRYBB1, CRYBB2, CRYBB3 and CRYBA4, all of which may be considered as candidate genes. Mutations in CRYBB1 have been shown to cause dominant congenital pulverulent cataract; mutations in CRYBB2 have been shown to cause dominant congenital cerulean blue and sutural cataract with punctate and cerulean opacities in humans. We are genotyping the remaining individuals in the full pedigree for the chromosome 22 markers, refining the localization, and sequencing candidate genes.
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