An autosomal recessive DNASE1L3-related autoimmune disease with unusual clinical presentation mimicking systemic lupus erythematosus

Lupus. 2017 Jun;26(7):768-772. doi: 10.1177/0961203316676382. Epub 2016 Nov 12.


We describe the third family in the world, after Arabian and Turkish ones, displaying an autosomal recessive autoimmune disease (AID), mimicking systemic lupus erythematosus (SLE), with unusual manifestations due to a homozygous frame-shift variant in DNASE1L3. SLE is a complex AID characterized by multiple organ involvement. Genetic risk variants identified account for only 15% of SLE heritability. Rare Mendelian forms have been reported, including DNASE1L3-related SLE. Through specific genetic tests we identified a homozygous 2 bp-deletion c.289_290delAC (NM_004944.2) in DNASE1L3, predicting frameshift and premature truncation (p.Thr97Ilefs*2). The same mutation was previously reported in three sisters, born from consanguineous parents and affected with hypocomplementemic urticarial vasculitis syndrome (HUVS). As approximately 50% of individuals affected with HUVS develop SLE, it is still unclear whether it is a SLE sub-phenotype or a separate condition.

Keywords: DNASE1L3; Systemic lupus erythematosus; hypocomplementemic urticarial vasculitis syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Autoimmune Diseases / diagnosis*
  • Autoimmune Diseases / genetics
  • Endodeoxyribonucleases / genetics*
  • Family
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / diagnosis*
  • Lupus Erythematosus, Systemic / genetics
  • Male
  • Middle Aged
  • Mutation
  • Syndrome
  • Urticaria / diagnosis
  • Urticaria / genetics
  • Vasculitis / diagnosis
  • Vasculitis / genetics


  • DNASE1L3 protein, human
  • Endodeoxyribonucleases