TLR9 and Spondyloenchondrodysplasia with immune dysregulation: On the other hand, biallelic loss-of-function mutations cause spondyloenchondrodysplasia with immune dysregulation (SPENCDI), a skeletal and neurological disorder with lupus-like symptoms and a type I interferon signature (31), in which TLR9 hyperactivation is suggested to cause immune dysregulation.