Suggestive Linkage of an Autosomal Dominant Cataract Locus (ADC 51) to Chromosome 19q

Abstract

Abstract: : Purpose: To map and identify the gene for ADC in a large Chilean family. Methods: ADC 51 is a three generation Chilean family with 6 affected individuals. SIMLINK analysis was used to estimate the power to detect linkage in this pedigree. We screened 16 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. Results: 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, 10, 11, 12, 13, 15, 16, 17, 19, 20, 21, and 22 and excluded all except for chromosome 19 based on lack of evidence of linkage or co-segregation. Markers on chromosome 19 yielded the highest LOD scores of 1.80 for D19s412, 1.52 for D19s223 and 1.52 for D19s178. Conclusions: Using our ADC screening panel, we excluded linkage in this family with markers known to be linked to human ADC except those on chromosome 19. We have demonstrated possible linkage of the locus in the ADC 51 family, the second in our laboratory, to chromosome 19. The ferritin light chain gene on chromosome 19 causes hyperferritinemia and is a candidate gene, as are the lens intrinsic membrane protein 2 (LIM2) and the myotonic dystrophy genes. The clinical features were not typical of hyperferritinemia. We are refining the localization and sequencing candidate genes.

Keywords: cataract • genetics • gene mapping