COG4 Variant and Saul-Wilson Syndrome

Saul-Wilson syndrome is a rare disease characterized by profound short stature of prenatal onset with lack of postnatal catch-up growth, characteristic radiographic findings and facial features, ocular manifestations such as lamellar cataracts and rod-cone dystrophy, neutropenia leading to frequent infections (particularly respiratory infections), and elevation of liver transaminases. The disease is caused by a recurrent amino acid substitution in COG4, a subunit of the octameric conserved oligomeric Golgi (COG) complex that participates in vesicular trafficking between the Golgi and endoplasmic reticulum (ER). The variant is known to cause accelerated vesicular trafficking from the Golgi to the ER, with a new steady-state equilibrium leading to decreased Golgi volumetrics. The abnormal glycosylation of proteoglycans is known to be at least partly related to the pathogenesis of the disease. This work summarizes the salient clinical manifestations of the disease, as well as the proposed mechanisms leading to its manifestations.