Study On The Mutation Of ADAR1 Gene In Dyschromatosis Symmetrica Hereditaria

Background: Dyschromatosis symmetrica hereditaria is a rare genodermatosis, which is characterized by autosomal dominant inheritance. Its symptoms are mixed hyperpigmented and hypopigmented macules on the dorsal aspect of the hands and feet and freckle-like macules on the face. The gene responsible for DSH has been identified as adenosine deaminase acting on RNA1(ADAR1), which maps to chromosome 1q21.3. ADAR1 gene encodes adenosine deaminase 1 acting on RNA1 / double-stranded RNAspecific adenosine deaminase( ADAR1/DSRAD). ADAR1/DSRAD catalyzes the deamination of adenosine to inosine in double-stranded RNA substrates, which results in the creation of alternative splicing sites or codon alternations that lead to functional changes in the protein. In recent years, novel mutations of ADAR1 gene were discovered and reported steadily and ceaselessly,which not only expand mutation spectrum of ADAR1 gene, but also built the foundation for the research on the relationship between phenotype and genotype, and the pathogenesis in DSH.Objective: To identify mutation of ADAR1 gene in two pedigrees and a sporadic case with Dyschromatosis symmetrica hereditaria(DSH).Methods: We have collected clinical data and blood samples from two pedigrees and a sporadic case with DSH in Sichuan province, China. And genomic DNA was extracted from the peripheral blood of these patients. All exons and its flanking sequences of ADAR1 gene were amplified by polymerase chain reaction(PCR), and the products of amplification were analyzed by direct sequencing method.Result: A novel frame-shift mutation c.2638delG(p.Asp880ThrfsX15) from the patients of the family1 was detected in the exon 8 of the ADAR1 gene; a novel missense mutation c.3109A>G(p.S1037G) was detected in the exon 12 of the ADAR1 gene from the family2.And a novel nonsense mutation c.2867C>A(p.S956X) was detected in the exon 10 of the ADAR1 gene from the sporadic case. Aforementioned three novel mutations were not found in unaffected family members and 100 unrelated healthy controls.Conclusion: The result suggests that the frame-shift mutation c.2638 del G(p.Asp880 Thrfs X15),the missense mutation c.3109A>G(p.S1037Gly) and the nonsense mutation c.2867C>A(p.S956X) in the ADAR1 gene may be the root cause of the disease in family1、family2 and the sporadic case with DSH respectively.