GENETIC-LINKAGE FOR DARIER DISEASE (KERATOSIS-FOLLICULARIS)

Darier disease is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion. Recent data have provided evidence fo r linkage of the Darier disease locus to 12q23-24.1 in British familie s. We have carried out linkage analysis using the 12q markers D12S58, D12S84, D12S79, D12SS6, PLA2, and D12S63 in 6 Canadian families. Pairw ise linkage analysis generated positive lod scores at all 6 markers at various recombination fractions, and each family showed positive lod scores with more than one marker. The peak led score in the multipoint analysis (Z(max)) was 5.5 in the interval between markers D12S58 and D12S84. These positive led scores in North American families of varied European ancestry confirm the location of the Darier disease gene, an d suggest genetic homogeneity. The future identification and sequencin g of the gene responsible for Darier disease should lead to improved u nderstanding of the disease and of keratinocyte adhesion in general. ( C) 1995 Wiley-Liss, Inc.