Localization Of DSH-associated Gene And Identification Of The Gene Mutation

Dyschromatosis symmetrica hereditaria(DSH) is a rare genodermatosis characterized by asymptomatic, symmetrical hyperpigmented and hypopigmented macules on the dorsum of extremities. The pathogenesis is still unknown. Effort to determine the gene responsible for the disease is made and the disease locus has been mapped recently to an 11.6 cM region on 1q11-1q21 between markers D1S2696 and D1S2635. More recently Miyamura et al has identified DSRAD as the disease gene. They found the gene mutation had occurred in four different Japanese DSH families.To localize and isolate the disease gene in Chinese DSH family, 2 DSH families from Jiangsu province of China have been studied by linkage analysis and mutation detection.6 STR DNA covering the gene locus have been selected to perform genotyping and linkage analysis. A cumulative maximum LOD score of 3.91 was obtained with marker D1S2343 at a recombination fraction 0 of 0.00. The result is strongly suggestive the linkage of the disease locus with 1q region which is consistent with the reported studies. Then DSRAD was sequenced as the most important candidate gene to detect the mutation in both families. The results showed that a CAA→TAA mutation within exon 2 occurred in pedigree 1. This nonsense mutation converts a glutamine codon to a terminate codon. The other family carried an "A" insertion within exon 6. This mutation lead to a frameshift and consequently terminated at amino acid 841. Both the mutations were not detected in the unaffected members and 50 normal controls.This study demonstrated that defects in DSRAD cause DSH in two Chinese families. This is the first report in Chinese literature and we described two novel mutations which are different from that found in Japanese DSH families.DSRAD encodes double-stranded RNA-specific adenosine deaminase (DSRAD) which site-selectively catalyzes the deamination of adenosine residue to inosine in the...