We have previously reported that Darier's disease gene (DAR) is located on chromosome 12 (12q23-24.1) between D12S84 and D12S354. We further analysed haplotype data for all kindreds and found that 3 individuals from 3 independent pedigrees showed recombinations at D12S129 and that 1 individual from a separate family showed recombination at D12S234, having narrowed the localization of the disease gene to a region of less than 3.8 cM between D12S234 and D12S129. By fluorescent in situ hybridization (FISH) analysis, the estimated physical distance between these two markers was 2-5 megabase. In addition, NO synthase 1, a candidate gene supposed to be in this region, was excluded from DAR by linkage analysis. We are now examining whether or not other candidate genes such as paxillin and serine/threonine protein phosphatase are truly located between D12S129 and D12S234 by two color FISH analysis.