Table 2 Genes involved in HSCR in humans and known mouse models of megacolon

Gene	Human					Mouse
Gene	Map location	Mode of inheritance	Phenotype in mutants	Penetrance of the HSCR trait	Refs	Natural mutant	Knockout	Refs
RET	10q11.2	AD	HSCR	70% in males and 50% in females for CDS mutations	43, 44, 60, 61	–	LRenal agenesis	82
GDNF	5p13	AD	HSCR	5 cases reportedLow penetrance	102–104	–	L	92–94
GDNF	5p13	AD	HSCR	5 cases reportedLow penetrance	102–104	–	Renal agenesis	92–94
NTN	19p13	AD	HSCR	1 case reported	105	–	–
SOX10	22q13	AD	WS4	About 80%	122–124	Dom (AD)	LCoat spotting	125
EDNRB	13q22	AR/AD	WS4/HSCR	Low	118, 126–129	s^l (AR)	SCoat spotting	117
EDN3	20q13	AR/AD	WS4/HSCR	1 case reported	130	ls (AR)	SCoat spotting	119
ECE1	1p36	AD	HSCR	1 case reported	131	–	SCoat spottingCraniofacial defects	132
ECE1	1p36	AD	CF and cardiac defect	1 case reported	131	–	SCoat spottingCraniofacial defects	132
ZFHX1B (SIP1)	2q22	AD	MCA-MR, facial gestal,	60%	133–135	–	Letal at gastrulation	136
PHOX2B	4p12	AD	CCHS	20%	137, 138	–	TIANo ANSVentilatory anomalies in Phox2b^+/−	139, 140
TCF4	18q21	AD	Epileptic encephalopathy	1 case	141–143	–	Early letalityAbnormal maturation of lymphocytes	144, 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; s^l, Piebald lethal; ls, lethal spotting; TIA, total intestinal aganglionosis.