Identification Of A Locus For Dyschromatosis Symmetrica Hereditaria By Genome-wide Scan

Background Dyschromatosis symmetrica hereditaria (DSH) (OMIM 127400) is also called reticulate acropigmentation of Dohi and symmetric dyschromatosis of the extremities. It is usually transmitted as an autosomal dominant pattern. But DSH has been reported that it could be also transmitted in an autosomal recessive form. It was first described by Toyama in a Japanese family in 1929. To data, most cases of DSH have been reported in the Japanese literature. Occurrence in families of other ethnic origins such as Chinese, Korean, Indian, England and South Americans had also been reported. There were no significant differences in clinical characteristics of the condition between cases from Japan and those from outside Japan. The main features of DSH are asymptomatic small macules scattered on the faces and hyperpigmented and hypopigmented macules on the dorsal aspects of the extremities, which appear in infancy or early childhood. The skin lesions commonly stop spreading before adolescence and last for life. The molecular basis of DSH is unknown. Kono et al. performed linkage analysis between DSH and microsatellite markers on chromosome 9 in three Japanese DSH families. But they obtained LOD scores of < -2 over the whole region of chromosome 9. Thus, they concluded that there was no linkage between DSH and chromosome 9. Up to date, the DSH disease gene and its chromosomal localization have not been identified yet. In this study, we undertook an entire genome-wide scan in two families with DSH identified in Anhui Province in China. Objective To identify a locus for dyschromatosis symmetrica hereditaria. Methods We performed a genome-wide search with 402 microsatellite markers in two large Chinese families to map the chromosome location of the responsible gene.LINKAGE software (5.10 Version) snd CYRILLIC software (2.02 Version) were used for linkage and haplotype analyses.Results We identified a locus at chromosome 1q11-1q21 with a cumulative maximum two-point LOD score of 8.85 at D1S2343 (9=0.00). Haplotype analyses indicate that the disease gene is located within 11.6cM region between markers D1 S2696 and D1 S2635. This is the first locus identified for the DSH. This study provides a map location for isolation of a disease gene causing DSH.Conclusion Chromosome 1q11-1q21 contains the disease gene of dyschromatosis symmetrica hereditaria. This is the first locus identified for the DSH. This studyprovides a map location for isolation of a gene causing DSH.