Along these lines, a curious aspect of the UFSP2 variant described here is that the V115E substitution results in central nervous system dysfunction but no obvious skeletal anomalies, while other UFSP2 variants result in autosomal dominant skeletal dysplasias but no seizures or defects in intellectual development.11–13 These previous reports, along with the observation of DDRGK1 variants in an autosomal recessive skeletal disorder (spondyloepimetaphyseal dysplasia, Shohat type, OMIM 616177) provide convincing evidence that UFMylation is required in the human skeletal system. The gene discussed is DDRGK1; the disease is spondyloepimetaphyseal dysplasia, matrilin-3 type.