Congenital Anomalies of the Kidney and Urinary Tract: A Genetic Disorder?

Table 2

Single-gene mutations associated with nonsyndromic human CAKUT.

Gene	Disease OMIM	Chromosome	Renal phenotype	Extrarenal phenotype	References
AGT	RTD	1p42	Reduced number of proximal tubules, short proximal tubules without brush border, atrophic loops of Henle and collecting ducts, closely packed glomeruli, marked thickening and disorganization of interlobular and preglomerular arteries	Large low-set ears, limb-positioning defects, arthrogryposis, lung hypoplasia, skull ossification defects	[29, 45]
AGTR1	RTD	3p24	Similar to AGT phenotype, PUV	Similar to AGT phenotype	[29, 45, 46]
AGTR2	—	Xq22-q23	UPJ obstruction, megaureter, MCDK hydronephrosis, PUV	—	[38–41, 47]
ACE	RTD	17q23.3	Similar to AGT phenotype renal hypodysplasia, PUV	Similar to AGT phenotype	[29, 45, 46]
BMP4	—	14q22-q23	Renal hypodysplasia	Cleft lip, microphthalmia	[48]
BMP7; Dlx5/Dlx6; p63	SHFM; #603273	3q27	Urethral malformations	Split-hand/split-foot malformation	[49]
CDC5L	—	46XX,t(6; 19); (p21; q13.1)	Multicystic kidney dysplasia	—	[50]
Eya1	BOR; #113650	8q12	Unilateral or bilateral renal agenesis renal hypodysplasia, VUR	Deafness, ear malformations branchial cysts	[51]
Fras1/; Fram2	Fraser syndrome	4q21; 13q13. 3	Renal agenesis/hypodysplasia	Ear and heart defects, syndactyly cryptophthalmos	[21, 51, 52]
FoxC1	—	6p25	CAKUT	—	[53]
Gata3	HDR syndrome; #146255	10pter	Renal dysplasia	Hypoparathyroidism sensorineural deafness	[54]
HNF1β/; TCF2	MODY5; #606391; RCAD; #137920; GCKD; #609886	17q12	Renal hypodysplasia, cysts	Diabetes	[20, 55, 56]
Pax2	Renal-coloboma; syndrome	10q24	Renal hypoplasia, VUR	Optic nerve coloboma branchyal cysts	[34, 57, 58]
Ren	RTD	17q23.3	Similar to AGT phenotype	Similar to AGT phenotype	[29, 45]
Ret	Renal agenesis; #191830	10q11.2	Absence of the kidney and ureter	Hirschsprung disease	[37]
Robo2	—	3p12.3	VUR	Limb and facial defects	[44, 59–61]
Six2	—	2p16-p15	Renal hypodysplasia	—	[48]
Slit2	—	4p15.2	Hydroureter, supernumerary UBs	—	[59]
Umod	MCDK2	16p12.3	Cysts in distal tubules and collecting ducts, renal dysplasia	—	[62, 63]
Upk3A	—	22q13.31	Renal agenesis/hypodysplasia	Facial and limb defects	[64, 65]
Usf2	—	46XX t(6;19); (p21; q13.1)	Multicystic kidney dysplasia	—	[66]
XPNPEP3	NPHP-like nephropathy	22q13.2	Renal cysts and dysplasia	—	[67]

AGTR: angiotensin II receptor type 1, AGTR2: angiotensin II receptor type 2, ARPKD: autosomal-recessive polycystic kidney disease, ADPKD: autosomal-dominant polycystic kidney disease, UPJ: ureteropelvic junction, VUR: vesicoureteral reflux, PUV: posterior urethral valves, UPJ: ureteropelvic junction, MCDK: multicystic dysplastic kidney, PUV: posterior urethral valve, RTD: renal tubular dysgenesis, RCAD: renal cysts and diabetes, MODY: maturity-onset diabetes, GCKD: glomerulocystic kidney disease, and NPHP: nephronophthisis, X-prolyl aminopeptidase (aminopeptidase P) 3, putative.