In a study using large-scale sequencing, sixteen individuals harboring de novo heterozygous variants in POLR2A, encoding RPB1, the largest subunit of Pol II, showed neurodevelopmental syndrome characterized by profound infantile-onset hypotonia and developmental delay, namely, neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities (NEDHIB) (Haijes et al., 2019). This evidence concerns the gene POLR2A and Global developmental delay.