Identification of a novel mutation in the DSRAD gene in a Chinese pedigree with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant skin disorder characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and dorsal aspects of the extremities that appear in infancy or early childhood. The DSH locus has recently been mapped to chromosome 1q21 and then pathogenic mutations have been identified in the DSRAD gene. In the study reported here we examined the DSRAD gene mutations of a three-generation Chinese pedigree with DSH by direct sequencing. We identified a novel heterozygous nucleotide T-->C transition at position 3388 in exon 14 of the DSRAD gene which induces a C1130R change in the putative deaminase domain of DSRAD. Our study expands the database on the DSRAD gene mutations in DSH and enriches the knowledge about the function of the DSRAD gene.

Two frameshift mutations in the RNA-specific adenosine deaminase gene associated with dyschromatosis symmetrica hereditaria.

OBJECTIVE: To report and analyze the mutations of the double-stranded RNA-specific adenosine deaminase (DSRAD) gene in 2 Chinese pedigrees with dyschromatosis symmetrica hereditaria (DSH). DESIGN: Pedigree study. SETTING: Anhui province of China. PATIENTS: Two Chinese families, consisting of 19 individuals (family 1) and 5 individuals (family 2). INTERVENTIONS: We directly performed mutation detection of the DSRAD gene in 2 Chinese families with DSH by sequencing. The whole coding region of DSRAD was amplified by polymerase chain reaction, and products were analyzed by direct sequencing. MAIN OUTCOME MEASURES: Frameshift DSRAD gene mutations. RESULTS: The c.3513insC (Arg1171fs) mutation was found in all patients but not in the healthy individuals from family 1, and the c.3220_3224delGCATC (Gly1073fs) mutation was found in 2 patients but not in the healthy members of family 2. These 2 mutations were not found in 96 unrelated control individuals. CONCLUSION: Our data suggest that these 2 novel frameshift mutations in the DSRAD gene could cause DSH in the Chinese Han population and add new variants to the repertoire of DSRAD mutations in DSH.

Seven novel mutations of the ADAR gene in Chinese families and sporadic patients with dyschromatosis symmetrica hereditaria (DSH).

Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules of on the extremities and caused by the mutations in the ADAR gene(also called DSRAD) encoding for RNA-specific adenosine deaminase. Here we reported clinical and molecular findings of 6 Chinese multi-generation families and 2 sporadic patients with DSH. We found that the same mutation could lead to different phenotypes even in the same family and we did not establish a clear correlation between genotypes and phenotypes. Seven novel heterozygous mutations of ADAR were identified, which were c.2433_2434delAG (p.T811fs), c.2197G>T (p.E733X), c.3286C>T (p.R1096X), c.2897G>T (p.C966F), c.2797C>T (p.Q933X), c.2375delT (p.L792fs) and c.3203-2A>G respectively. Our data add new variants to the repertoire of ADAR mutations in DSH.