Mutational spectrum of the ADAR1 gene in dyschromatosis symmetrica hereditaria

Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the extremities and caused by the mutations of adenosine deaminase acting on RNA1 (ADAR1) gene. We screened 14 unrelated families or sporadic cases for mutation in the full coding sequence of this gene. Eight novel heterozygous mutations of ADAR1 and four known mutations were identified, including four missense mutations (p.R26K, p.Y1192D, p.R916Q, p.R1155W), six frameshift mutations (p.N205fsX217, p.V211fsX217, p.V404fsX417, p.I914fsX927, p.L1053fsX1076, p.L1070fs1092), and two nonsense mutations (p.R474X, p.R1096X). Interestingly, we failed to detect any mutations of ADAR1 in one family. Including our data, there are now 93 different mutations reported in 105 independent patients that we have tabulated. From the review of clinical features in these reports, we found that the same mutation could lead to different phenotypes even in the same family and did not establish a clear correlation between genotypes and phenotypes. Finally this study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ADAR1 gene.