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D. Burch, L. Richter, F. Barría von Bischhoffshausen, P. Flodman, M. Spence, J. Bateman; Mapping of an Autosomal Dominant Cataract (ADC) in a Chilean Family to Chromosome 3q . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2522.
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© ARVO (1962-2015); The Authors (2016-present)
To map and identify the gene for autosomal dominant cataracts (ADC) in a large Chilean family.
ADC51 is a three–generation Chilean family with six affected individuals. Clinically, affected individuals had a broad range of cataract phenotype with embryonal, punctate opacities, posterior subcapsular cataracts and complete, white opacification of the lens. SIMLINK analysis was used to estimate the power to detect linkage in this pedigree. We screened 15 affected and unaffected members with a panel of markers for known ADC loci using PCR amplification 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 the LIPED. We initially sequenced the beaded filament gene (BFSP2) and found all sequences to match the reference. PCR primers were designed for exons 1, 2, 3, 4, and 6 including the intron/exon borders of the calcium sensing receptor (CASR) gene, while previously designed primers for exon 5 and the corresponding intron/exon borders were used (Pollak et. al, 1993). We sequenced PCR products using the ABI dye terminator kit v1.1 and an ABI 3100 Avant DNA sequencer (Applied Biosystems, Foster City, CA.)
For a tightly–linked marker, we estimated that linkage analysis in this family will have 48% power to detect a LOD greater than 2; the maximum LOD score achieved over 1000 simulations was 2.96. We calculated LOD scores between the ADC 51 locus and markers on chromosomes 1, 2, 3, 10, 11, 12, 13, 15, 16, 17, 19, 20, 21, and 22 and excluded all except for chromosome 3 based on lack of evidence of linkage or co–segregation. Markers on chromosome 3 yielded the highest LOD score of 2.71 for D3S1267. We have high–quality sequence for exons 1 through 5 and all are identical to the reference. Exon 6 is partially completed and preliminary results show 3 previously–reported untranslated SNPs (db Build #35.1; refSNP ID’s: rs4677948, rs6438718, & rs3182100) and one translated SNP (db Build #35.1; refSNP ID: rs1801726 GLU –> Gln) in both affected and unaffected individuals.
Using our ADC screening panel, we excluded linkage in this family with markers known to be linked to human ADC except those on chromosome 3. We mapped cataract gene to chromosome 3q21–q22, near the CASR gene. We are sequencing the remaining portion of exon 6 for a mutation which segregates with the disease.
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