Al-Mayouf et al. (2011) aimed to identify an autosomal recessive form of SLE.  To do so, they recruited subjects with healthy consanguineous parents and at least two affected siblings.  Seven such families were recruited to the study.  All patients had a pediatric onset of the disorder, a high frequency of anti-neutrophil cytoplasmic antibodies and lupus nephritis.  Autozygome analysis and linkage analysis helped identify overlapping autozygous intervals on chromosome 3p14.3 (lod score 6.6) in six of the families.  As DNASE1L3 was a promising gene in this region, it was sequenced and a homozygous 1-bp deletion c.643delT (p.Trp215GlyfsX2) was discovered.  The deletion was found in all affected members of the six families and haplotype analysis confirmed it to be a founder mutation.  Exome sequencing on two patients did not find any coding variants of functional consequence, thus ruling out the possibility of the mutation being a mere ‘tag’ on the ancestral haplotype block.  The mutation was not found in 192 ethnically-matched controls, the 1000 Genomes Project or the Exome Variant Server and was predicted to be pathogenic.  Lymphoblast cell lines created from two of the patients had no detectable DNASE1L3 transcript, presumably due to nonsense mediated decay.  Also, a nicking assay showed that the protein encoded by the mutant DNASE1L3 lacked DNase activity.  A total of 85 patients with sporadic SLE were also genotyped and one individual was found to be homozygous for an R206C substitution.  While this mutation has been shown experimentally to abolish DNase activity, larger studies are required to confirm this link.