Variants in the human double-stranded RNA editing enzyme ADAR produce three well-characterized rare Mendelian Diseases: Dyschromatosis Symmetrica Hereditaria (OMIM: 127400), Aicardi-Goutières syndrome (OMIM: 615010) and Bilateral Striatal Necrosis/Dystonia.
The findings of this study expand our knowledge of the range of ADAR1 gene mutations in DSH and will contribute to identifying correlations between the various DSH phenotypes and genotypes.
A three-generation family exhibiting phenotypic variability with a single germline ADAR1 mutation suggests that chilblain might aggravate the clinical phenotypes of DSH.
Two novel DSRAD mutations, p.G1047D and p.Y587C, were found in Chinese patients with DSH and our data add new variants to the knowledge of DSRAD mutations in DSH.
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.
A Chinese family with typical DSH was screened for mutation of ADAR1, and we aimed to investigate the functional significance of the identified mutation.
We performed a mutation analysis of the ADAR1 gene in 2 Chinese families with DSH and reviewed all articles published regarding ADAR1 mutations reported since 2003 by using PubMed.
Because ADAR1 plays various important roles in human tissue, we believe that a clarification of the pathogenesis of DSH will promote the understanding of the physiological functions of ADAR1, which will have significant scientific implications.
Our study suggests that splice site mutation IVS5-1g>a and missense mutation p.R1026W are new mutations of ADAR1 gene, which should be useful in genetic counseling and prenatal diagnosis for the affected families and expanding the database on ADAR1 gene mutations in DSH.
Six novel mutations were found in five unrelated families and one sporadic case, which have further improved our understanding on the role of ADAR1 in DSH.
Six novel mutations of the ADAR1 gene in patients with dyschromatosis symmetrica hereditaria: histological observation and comparison of genotypes and clinical phenotypes.
DSH was mapped to chromosome 1q21.3, and mutations in the gene ADAR (DSRAD) were identified in Japanese, Chinese and Taiwanese families with autosomal dominant DSH.
Only three cases with neurological disorders have been reported, although more than 50 mutations of the ADAR1 gene causing DSH have been reported and none of them had any neurological symptoms.