Table 4

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

Gene		Human				Mouse
Gene		Map location	Mode of inheritance			Phenotype in mutants	Frequence of mutation in heterozygotes	Refs	Natural mutant	Knock-out	Refs
RET		10q11.2		AD		HSCR		50% familial cases	119			—		L	108
RET		10q11.2		AD		HSCR		15% sporadic cases	119			—		Renal agenesis	108
GDNF		5p13		AD		HSCR		5 cases		31, 142, 143			—		L	132–134
GDNF		5p13		AD		HSCR		5 cases		31, 142, 143			—		Renal agenesis	132–134
NTN	19p13	AD	HSCR	1 case	144		—	—
SOX10		22q13		AD		WS4				57, 59, 165			Dom(AD)		L	164
SOX10		22q13		AD		WS4				57, 59, 165			Dom(AD)		Coat spotting	164
EDNRB		13q22		AR/AD		WS4/HSCR		5%		53, 157–160			s^l (AR)		S	154
EDNRB		13q22		AR/AD		WS4/HSCR		5%		53, 157–160			s^l (AR)		Coat spotting	154
EDN3		20q13		AR/AD		WS4/HSCR		<5%		156			ls(AR)		S	155
EDN3		20q13		AR/AD		WS4/HSCR		<5%		156			ls(AR)		Coat spotting	155
ECE1		1p36		AD		HSCR	1 case		162			—		S	161
						CF and cardiac defect								Coat spotting
						CF and cardiac defect								CF defects
SIP1	2q22	Spo	HSCR, MR, facial dysmorphism	6 cases	38, 39, 41		—	—	—

AD: autosomal dominant, AR: autosomal recessive, Spo: sporadic,s^l: Piebald lethal, ls: lethal spotting, S: short segment megacolon, L: long segment megacolon, CF: craniofacial, MR: mental retardation.