incrementalTreatment update
JAK inhibition shows partial response in DNASE1L3-deficient HUVS
Hypocomplementemic Urticarial Vasculitis Syndrome →Summary
A 2026 case report described partial improvement with JAK inhibition in a patient with compound heterozygous DNASE1L3 variants who was refractory to multiple immunosuppressive agents. This represents a novel therapeutic approach for refractory HUVS.
Related genes
DNASE1L3c.289_290delAC (frameshift)
First identified genetic cause of familial HUVS. Homozygous frameshift mutation causes complete loss of endonuclease activity via nonsense-mediated mRNA decay. Impairs clearance of extracellular chromatin from apoptotic cells.DNASE1L3c.320+4delAGTA (splice-site)
Second identified DNASE1L3 mutation in an unrelated HUVS family. Causes exon skipping and abolished endonuclease activity as demonstrated by plasmid nicking assay.DNASE1L3c.572A>G, p.Asn191Ser
Novel variant that does not affect enzyme production but impairs secretion. DNASE1L3 191S protein is overexpressed intracellularly but absent in supernatant, demonstrating a distinct loss-of-function mechanism.More from Hypocomplementemic Urticarial Vasculitis Syndrome
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ID: hypocomplementemic-urticarial-vasculitis-syndrome-update-5Type: treatment_updateImpact: incremental