title: DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome.
abstract: OBJECTIVE
  Hypocomplementemic urticarial vasculitis syndrome (HUVS) is characterized by recurrent urticaria along with dermal vasculitis, arthritis, and glomerulonephritis. Systemic lupus erythematosus (SLE) develops in >50% of patients with HUVS, although the pathogenesis is unknown. The aim of this study was to identify the causative DNA mutations in 2 families with autosomal-recessive HUVS, in order to reveal the pathogenesis and facilitate the laboratory diagnosis.
  
  
  METHODS
  Autozygosity mapping was combined with whole-exome sequencing.
  
  
  RESULTS
  In a family with 3 affected children, we identified a homozygous frameshift mutation, c.289_290delAC, in DNASE1L3. We subsequently identified another homozygous DNASE1L3 mutation leading to exon skipping, c.320+4delAGTA, in an unrelated family. The detected mutations led to loss of function, via either nonsense-mediated messenger RNA decay or abolished endonuclease activity, as demonstrated by a plasmid nicking assay.
  
  
  CONCLUSIONS
  These results show that HUVS is caused by mutations in DNASE1L3, encoding an endonuclease that previously has been associated with SLE.
authors.affiliation: Ankara University School of Medicine, Ankara, Turkey.
authors.forename: Z Birsin
authors.initials: ZB
authors.lastname: Ozçakar
authors.forename: Joseph
authors.initials: J
authors.lastname: Foster
authors.forename: Oscar
authors.initials: O
authors.lastname: Diaz-Horta
authors.forename: Ozgur
authors.initials: O
authors.lastname: Kasapcopur
authors.forename: Yao-Shan
authors.initials: YS
authors.lastname: Fan
authors.forename: Fatoş
authors.initials: F
authors.lastname: Yalçınkaya
authors.forename: Mustafa
authors.initials: M
authors.lastname: Tekin
mesh_terms: D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003165:Complement System Proteins / Q000172:deficiency*; D004252:DNA Mutational Analysis; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D008297:Male; D009154:Mutation; D014581:Urticaria / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D014657:Vasculitis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology
chemical_list: D003165:Complement System Proteins; C485421:DNASE1L3 protein, human; D004706:Endodeoxyribonucleases