significantGenetic finding
DNASE1L3 mutations identified as cause of familial HUVS
Hypocomplementemic Urticarial Vasculitis Syndrome →Summary
Özçakar et al. (2013) identified biallelic DNASE1L3 loss-of-function mutations in two families with autosomal recessive HUVS, establishing the first known genetic cause. Mutations abolish endonuclease activity, impairing extracellular DNA clearance from apoptotic cells.
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.Source
Grade Acohort
DNASE1L3 mutations in hypocomplementemic urticarial vasculitis syndrome
Özçakar ZB, Foster J 2nd, Diaz-Horta O, Kasapcopur O, Fan YS, Yalçınkaya F, Tekin M · Arthritis Rheum · 2013
- •Identified DNASE1L3 loss-of-function mutations as the genetic cause of familial HUVS
- •Homozygous frameshift mutation c.289_290delAC in one family
- •Autosomal recessive inheritance pattern established
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ID: hypocomplementemic-urticarial-vasculitis-syndrome-update-0Type: genetic_findingImpact: significant