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Background  Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominantly inherited skin disease associated with mutations of  ADAR1 , the gene that encodes a double-stranded RNA-specific adenosine deaminase. The purpose of this study was to investigate the potential mutations in  ADAR1  in seven Chinese families with DSH.    Methods  All the coding exons including adjacent intronic as well as 5′ and 3′ untranslated region (UTR) of  ADAR1  were screened by direct sequencing. Moreover, quantitative reverse-transcription polymerase chain (qRT-PCR) and Western blot were applied to determine the pathogenic effects associated with the mutations.    Results  Molecular genetic investigations detected five novel mutations (c.556C > T, c.3001C > T, c.1936_1937insTG, c.1065_1068delGACA and c.1601G > A resulting in p.Gln186X, p.Arg1001Cys, p.Phe646LeufsX16, p.Asp357ArgfsX47 and p.Gly471AspfsX30 protein changes, respectively) as well as two previously reported (c.2744C > T and c.3463C > T causing p.Ser915Phe and p.Arg1155Trp protein changes, respectively). Among them, we found that the substitution c.1601G > A at the last nucleotide of exon 2 compromised the recognition of the splice donor site of intron 2, inducing an aberrant transcript with 190-bp deletion in exon 2 and causing an approximately 50% reduction of  ADAR1  mRNA level in affected individual. In addition, consistent with the predicted results, the expression patterns of other novel mutations were detected by Western blot.    Conclusion  We identified five novel and two recurrent mutations of the  ADAR1  gene in seven Chinese families with DSH and investigated potential effects of the novel mutations in this study. Our study expands the database on mutations of  ADAR1  and for the first time, demonstrates the importance of exonic nucleotides at exon-intron junctions for  ADAR1  splicing.

Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria