title: Five novel mutations in the ADAR1 gene associated with dyschromatosis symmetrica hereditaria.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Wu
authors.forename: Lihua
authors.initials: L
authors.lastname: Cao
authors.forename: Qingzhu
authors.initials: Q
authors.lastname: Tang
authors.forename: Xuesha
authors.initials: X
authors.lastname: Xing
authors.forename: Hongwei
authors.initials: H
authors.lastname: Ma
authors.forename: Shifa
authors.initials: S
authors.lastname: Zhang
authors.affiliation: The Research Center for Medical Genomics, MOH Key Laboratory of Cell Biology and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China. luoyang@mail.cmu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D010859:Pigmentation Disorders / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D012326:RNA Splicing; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA
chemical_list: D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase