DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome

Z. Birsin Özçakar, Joseph Foster, Oscar Diaz-Horta, Ozgur Kasapcopur, Yao Shan Fan, Fatoş Yalçinkaya, Mustafa Tekin

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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. Conclusion These results show that HUVS is caused by mutations in DNASE1L3, encoding an endonuclease that previously has been associated with SLE.

Original languageEnglish (US)
Pages (from-to)2183-2189
Number of pages7
JournalArthritis and Rheumatism
Volume65
Issue number8
DOIs
StatePublished - Aug 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)

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