In conclusion, our results support that aberrant CpG hypermethylation at least partly accounts for GFRA4 silencing in HSCR, which impairs its protective role in enteric nervous system.
To support the role of PSPN R91C in HSCR phenotype, enteric nervous system (ENS) progenitors were isolated from human postnatal gut tissues and expression of GFRα4, the main co-receptor for PSPN, was demonstrated.