PSMC5 and Global developmental delay: With the exception of the PSMC5 variant, our findings agree with the notion that the CANDLE/PRAAS phenotype that presents with prominent neutrophilic panniculitis, systemic inflammation, and, in some instances, cognitive delay is mostly caused by loss-of-function mutations in the 20S proteasome subunits or in proteins that mediate proteasome assembly (11–18, 35).