Combined with these in vivo and in vitro data and considering that previous studies have proven that normal programmed apoptosis of HZ cells in the growth plate is a critical process in mouse development 49-51, instead of the critical and classical pathways to modulate SOX9, our study provided a new opinion to elucidate the mechanism of SEMD caused via DDRGK1 mutation. Here, SOX9 is linked to spondyloepimetaphyseal dysplasia.