RET and Hirschsprung disease: Previous genome-wide linkage/association studies have identified several modifier genes in different genomic regions, but RET is the only gene known to play a major role in all forms of HSCR susceptibility and a quantitative study of its allelic spectrum should provide clues on the role of both rare and common sequence variants in the complex inheritance of HSCR, particularly its relationships to factors that are correlated with risk, such as gender.