incrementalNew research
Novel DNASE1L3 variant in Emirati families demonstrates secretion defect mechanism
Hypocomplementemic Urticarial Vasculitis Syndrome →Summary
A novel DNASE1L3 variant (c.572A>G, p.Asn191Ser) was identified in three Emirati families with SLE/HUVS overlap. Unlike previous mutations that ablate protein production, this variant impairs enzyme secretion, expanding our understanding of DNASE1L3 loss-of-function mechanisms.
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-4Type: new_researchImpact: incremental