With 58 DNMs (50 missense, 3 indel, 2 splice site, 2 initiator codon and 1 frameshift) in genes of the V-ATPase complex identified in exome sequence data from over 30 000 individuals with severe DD,31 and significant association with severe DD for 2 genes of this group (ATP6V0A1 and ATP6V1A) out of 281, we propose that a V-ATPase-related disease should be considered in individuals presenting with mild-to-profound developmental delays and epilepsy, with or without microcephaly. This evidence concerns the gene ATP6V1A and Global developmental delay.