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

We describe the third family in the world, after Arabian and Turkish ones, displaying an\r\nautosomal recessive autoimmune disease (AID), mimicking systemic lupus erythematosus\r\n(SLE), with unusual manifestations due to a homozygous frame-shift variant in\r\nDNASE1L3. SLE is a complex AID characterized by multiple organ involvement. Genetic\r\nrisk variants identified account for only 15% of SLE heritability. Rare Mendelian forms have\r\nbeen reported, including DNASE1L3-related SLE.\r\nThrough specific genetic tests we identified a homozygous 2 bp-deletion c.289_290delAC\r\n(NM_004944.2) in DNASE1L3, predicting frameshift and premature truncation\r\n(p.Thr97Ilefs*2). The same mutation was previously reported in three sisters, born from consanguineous\r\nparents and affected with hypocomplementemic urticarial vasculitis syndrome\r\n(HUVS). As approximately 50% of individuals affected with HUVS develop SLE, it is still\r\nunclear whether it is a SLE sub-phenotype or a separate condition. Lupus (2016) 0, 1–5.