Positional cloning of the gene causing Dyschromatosis Symmetrica Hereditaria

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Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary disorder, first reported by Toyama in 1910. It is characterized by a mixture of hypopigmented and hyperpigmented macules of various sizes on the backs of the hands and feet. To DSH locus, we tried an entire genome-wide scan using 343 microsatellite markers for linkage analysis and haplotype analysis was carried out in the three families with DSH, and the results suggested that the gene responsible for DSH lies in the interval of approximately 500kb which was bound proximally by the IL6R gene and distally by the KCNN3 gene at chromosome 1q21.3. Between those two genes, seven genes have been mapped on the Entrez Map View, NCBI web site. Four affected individuals from each of Pedigrees 1,2 and 3,and of Pedigree 4 were screened by SSCP, which revealed mutant heteroduplexes made by hybridizing PCR fragments of The RNA-specific adenosine deaminase (DSRAD) genes. Direct sequence analysis of the PCR products showed that they were heterozygous for mutations of R474X, L923P, K952X and F11655 in Pedigrees 1,2,3 and 4,respectively. The mutations involved in causing DSH have been identified in the gene that encodes DSRAD as the disease gene.