DNASE1L3 Mutations in Hypocomplementemic Urticarial Vasculitis Syndrome
ZB Özçakar, J Foster, O Diaz‐Horta… - Arthritis & …, 2013 - Wiley Online Library
Arthritis & Rheumatism, 2013•Wiley Online Library
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 …
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 …
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.
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