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 journalArticle

51 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 1 2013

ASJC Scopus subject areas

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

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    Özçakar, Z. B., Foster, J., Diaz-Horta, O., Kasapcopur, O., Fan, Y. S., Yalçinkaya, F., & Tekin, M. (2013). DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome. Arthritis and Rheumatism, 65(8), 2183-2189. https://doi.org/10.1002/art.38010