Neurodevelopmental defects in human cortical organoids with -acetylneuraminic acid synthase mutation.

Biallelic genetic variants in -acetylneuraminic acid synthase (), a critical enzyme in endogenous sialic acid biosynthesis, are clinically associated with neurodevelopmental disorders. However, the mechanism underlying the neuropathological consequences has remained elusive. Here, we found that mutation resulted in the absence of both sialic acid and protein polysialylation in the cortical organoids and notably reduced the proliferation and expansion of neural progenitors.