Why do Down Syndrome patients have high risk of Hirschsprung disease?

Chakravarti, AravindaChatterjee, SumantraDavoli, Teresa

Summary​

We introduce a human genetics-cum-experimental paradigm for uncovering the genetic mechanisms by which increased chromosome 21 dosage leads to associations of specific diseases in Down Syndrome (DS), specifically, Hirschsprung disease (HSCR). Here we dissect the causal factors increasing HSCR susceptibility, specifically how RET enhancer variants that decrease its expression are further compromised by increased dosage of chromosome 21, likely through SOD1 and other chromosome 21 genes.