title: The adenosine deaminase acting on RNA 1 p150 isoform is involved in the pathogenesis of dyschromatosis symmetrica hereditaria.
abstract: BACKGROUND
  Dyschromatosis symmetrica hereditaria (DSH) is characterized by the presence of hyperpigmented and hypopigmented macules mostly on the dorsal aspects of the extremities. Mutations in the adenosine deaminase acting on RNA1 (ADAR1) gene have been revealed as the cause of DSH. ADAR1 is known to give rise to two protein isoforms (p150 and p110) that differ by the 295 N-terminal amino acids, but the specific roles of its two isoforms in the pathogenesis of DSH are poorly understood.
  
  
  OBJECTIVE
  A Chinese family with typical DSH was screened for mutation of ADAR1, and we aimed to investigate the functional significance of the identified mutation.
  
  
  METHODS
  All exons and adjacent exon-intron sequences were amplified and sequenced. The possible influence of the identified mutation on the functionality of p150 and p110 was analysed using the minigene strategy and dual-luciferase reporter assay, respectively.
  
  
  RESULTS
  We identified a novel two-base-pair deletion of AG (c.271_272delAG) in exon 2 of ADAR1. The AG deletion caused a frameshift mutation in the p150 isoform, and the mutant p150 transcripts were subjected to nonsense-mediated mRNA decay. However, the deletion mutation did not alter the encoded amino acid sequence of the p110 protein due its position in the 5'-untranslated region of the p110 isoform, and had no significant influence on the expression of p110.
  
  
  CONCLUSIONS
  The results represent the first evidence that the ADAR1 p150 isoform is the determinant of DSH and may give insight into the currently unknown mechanisms involved in the development of DSH.
authors.affiliation: Children's Hospital and Institutes of Biomedical Sciences, Fudan University, 130 Dong-An Road, Shanghai 200032, China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhang
authors.forename: X D
authors.initials: XD
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: H L
authors.initials: HL
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: X Z
authors.initials: XZ
authors.lastname: Zhao
authors.forename: W
authors.initials: W
authors.lastname: Cao
authors.forename: Q H
authors.initials: QH
authors.lastname: Xing
authors.forename: F M
authors.initials: FM
authors.lastname: Shao
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008297:Male; D010375:Pedigree; D010859:Pigmentation Disorders / Q000151:congenital* / Q000201:enzymology / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics; D016601:RNA-Binding Proteins
chemical_list: D020033:Protein Isoforms; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase