Interestingly, a distinct PHOX2B missense variant at this position (R44G) was found to be associated with neuroblastoma with Hirschsprung disease (Trochet et al., 2004), and this variant was previously found to decrease binding to monomer DNA sites (Trochet, Hong, et al., 2005). This evidence concerns the gene PHOX2B and Hirschsprung disease.