Table 2 Genes involved in HSCR in humans and known mouse models of megacolon
Map locationMode of inheritancePhenotype in mutantsPenetrance of the HSCR traitRefsNatural mutantKnockoutRefs
RET10q11.2ADHSCR70% in males and 50% in females for CDS mutations43, 44, 60, 61LRenal agenesis82
GDNF5p13ADHSCR5 cases reportedLow penetrance102–104L92–94
Renal agenesis
NTN19p13ADHSCR1 case reported105
SOX1022q13ADWS4About 80%122–124Dom (AD)LCoat spotting125
EDNRB13q22AR/ADWS4/HSCRLow118, 126–129sl (AR)SCoat spotting117
EDN320q13AR/ADWS4/HSCR1 case reported130ls (AR)SCoat spotting119
ECE11p36ADHSCR1 case reported131SCoat spottingCraniofacial defects132
CF and cardiac defect
ZFHX1B (SIP1)2q22ADMCA-MR, facial gestal,60%133–135Letal at gastrulation136
PHOX2B4p12ADCCHS20%137, 138TIANo ANSVentilatory anomalies in Phox2b+/−139, 140
TCF418q21ADEpileptic encephalopathy1 case141–143Early letalityAbnormal maturation of lymphocytes144, 145
  • AD, autosomal dominant; ANS, autonomic nervous system; AR, autosomal recessive; CF, craniofacial; L, long-segment megacolon; MR, mental retardation; S, short-segment megacolon; Spo, sporadic; sl, Piebald lethal; ls, lethal spotting; TIA, total intestinal aganglionosis.