Fig. 9: A model describing the effects of C19F MGP expression on the growth plate.

The C19F variant in MGP results in the impaired processing of the signal peptide and the retention of the mutated protein in the ER. This in turn leads to ER stress and markedly increased deaths of the growth plate prehypertrophic/hypertrophic cells which are known to express MGP at high levels. The cellular alterations may affect the expression and secretion of WT MGP causing the premature closure of the growth plates and the associated skeletal anomalies.