SEC24C deficiency causes trafficking and glycosylation abnormalities in an epileptic encephalopathy with cataracts and dyserythropoeisis

As a major component of intracellular trafficking, the coat protein complex II (COPII) is indispensable for cellular function during embryonic development and throughout life. The four SEC24 proteins (A-D) are essential COPII components involved in cargo selection and packaging. A human disorder corresponding to alterations of SEC24 function is currently only known for SEC24D. Here, we report that biallelic loss of SEC24C leads to a syndrome characterized by primary microcephaly, brain anomalies, epilepsy, hearing loss, liver dysfunction, anemia, and cataracts in an extended consanguineous family with four affected individuals. […] Moreover, a shift in the N-glycosylation pattern and deregulation of the N-glycosylation pathway suggest a possible secondary alteration of protein glycosylation, linking the described disorder with the congenital disorders of glycosylation.