de novo missense mutations in dhx30 impair global translation and cause a neurodevelopmental disorder dhx30 is a member of the family of dexhbox helicases which use atp hydrolysis to unwind rna secondary structures here we identified six different de novo missense mutations in dhx30 in twelve unrelated individuals affected by global developmental delay gdd intellectual disability id severe speech impairment and gait abnormalities while four mutations are recurrent two are unique with one affecting the codon of one recurrent mutation all amino acid changes are located within highly conserved helicase motifs and were found to either impair atpase activity or rna recognition in different in vitro assays moreover protein variants exhibit an increased propensity to trigger stress granule sg formation resulting in global translation inhibition thus our findings highlight the prominent role of translation control in development and function of the central nervous system and also provide molecular insight into how dhx30 dysfunction might cause a neurodevelopmental disorder