Physical and transcriptional map of the critical region for keratolytic winter erythema (KWE) on chromosome 8p22-p23 between D8S550 and D8S1759

Keratolytic winter erythema is an autosomal dominant skin disorder characterised by erythema, hyperkeratosis, and peeling of the skin of the palms and soles, especially during winter. The keratolytic winter erythema locus has been mapped to human chromosome 8p22-p23. This chromosomal region has also been associated with frequent loss of heterozygosity in different types of cancer. To identify positional candidate genes for keratolytic winter erythema, a BAC contig located between the markers at D8S550 and D8S1695 was constructed and sequenced. It could be extended to D8S1759 by a partially sequenced BAC clone identified by database searches. In the 634 404 bp contig 13 new polymorphic microsatellite loci and 46 single nucleotide and insertion/deletion polymorphisms were identified. Twelve transcripts were identified between D8S550 and D8S1759 by exon trapping, cDNA selection, and sequence analyses. They were localised on the genomic sequence, their exon/intron structure was determined, and their expression analysed by RT-PCR. Only one of the transcripts corresponds to a known gene, encoding B-lymphocyte specific tyrosine kinase, BLK. A putative novel myotubularin-related protein gene (MTMR8), a potential human homologue of the mouse acyl-malonyl condensing enzyme gene (Amac1), and two transcripts showing similarities to the mouse L-threonine 3-dehydrogenase gene and the human SEC oncogene, respectively, were identified. The remaining seven transcripts did not show similarities to known genes. There were no potentially pathogenic mutations identified in any of these transcripts in keratolytic winter erythema patients.