Genetics of congenital anomalies of the kidney and urinary tract.
Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 1 in 500 births and are a major cause of morbidity in children. Notably, CAKUT account for the most cases of pediatric end-stage renal disease and predispose the individual to hypertension and cardiovascular disease throughout life. Although some forms of CAKUT are a part of a syndrome or are associated with a positive family history, most cases of renal system anomalies are sporadic and isolated to the urinary tract. Broad phenotypic spectrum of CAKUT and variability in genotype-phenotype correlation indicate that pathogenesis of CAKUT is a complex process that depends on interplay of many factors. This review focuses on the genetic mechanisms (single-gene mutations, modifier genes) leading to renal system anomalies in humans and discusses emerging insights into the role of epigenetics, in utero environmental factors, and micro-RNAs (miRNAs) in the pathogenesis of CAKUT. Common gene networks that function in defined temporospatial fashion to orchestrate renal system morphogenesis are highlighted. Derangements in cellular, molecular, and morphogenetic mechanisms that direct normal renal system development are emphasized as a major cause of CAKUT. Integrated understanding of how morphogenetic process disruptions are linked to CAKUT will enable improved diagnosis, treatment, and prevention of congenital renal system anomalies and their consequences.
Song
Renfang
R
Section of Pediatric Nephrology, Department of Pediatrics, Hypertension and Renal Center of Excellence, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Yosypiv
Ihor V
IV
D000818:Animals; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D009024:Morphogenesis / Q000235:genetics; D010641:Phenotype; D012084:Renin-Angiotensin System / Q000235:genetics; D014551:Urinary Tract / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D014564:Urogenital Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
J Med Genet. 2002 Dec;39(12):882-92
12471200
Development. 2007 Feb;134(4):801-11
17229764
PLoS Genet. 2010 Jan 15;6(1):e1000809
20084103
Development. 1995 Mar;121(3):867-75
7720589
Nephron Exp Nephrol. 2005;99(1):e1-8
15637462
Am J Pathol. 1996 Dec;149(6):2067-79
8952539
Kidney Int. 2007 Mar;71(6):574-81
17245395
Development. 2010 Mar;137(5):755-65
20110314
Am J Hum Genet. 2008 Feb;82(2):344-51
18252215
Development. 2009 Dec;136(23):3979-89
19906865
Pharmacoepidemiol Drug Saf. 2003 Dec;12(8):633-46
14762979
J Am Soc Nephrol. 1999 Oct;10(10):2125-34
10505689
Kidney Int. 1997 Sep;52(3):811-6
9291203
Pediatr Nephrol. 2002 Dec;17(12):1021-6
12478351
Tokai J Exp Clin Med. 2003 Oct;28(3):121-6
15055404
Pediatr Nephrol. 2009 Aug;24(8):1501-8
19350278
Nature. 1994 Dec 15;372(6507):679-83
7990960
J Am Soc Nephrol. 2010 Mar;21(3):460-7
20056748
Pediatr Res. 2004 Dec;56(6):988-93
15470205
Am J Physiol. 1998 Dec;275(6):F938-45
9843911
Nat Genet. 2002 Sep;32(1):109-15
12195422
J Clin Invest. 2010 Mar;120(3):791-802
20179356
Semin Fetal Neonatal Med. 2008 Jun;13(3):125-32
18096451
Clin Biochem. 2010 Jan;43(1-2):71-5
19781541
Pediatr Nephrol. 2009 Aug;24(8):1569-72
19255789
Pediatr Nephrol. 2009 Jun;24(6):1151-7
19184120
Mech Dev. 2010 Jan-Feb;127(1-2):21-7
19961928
Organogenesis. 2009 Jan;5(1):306-14
19568352
Nat Genet. 2005 Oct;37(10):1082-9
16186816
Genes Dev. 1996 Jun 15;10(12):1467-78
8666231
J Am Soc Nephrol. 2007 May;18(5):1566-75
17409309
FASEB J. 1989 Aug;3(10):2141-50
2666230
EMBO J. 2004 Apr 7;23(7):1657-68
15029248
Eur J Hum Genet. 2005 Jun;13(6):789-92
15785774
Pediatr Nephrol. 2009 Jan;24(1):55-60
18846391
Development. 2005 Feb;132(3):529-39
15634693
J Am Soc Nephrol. 2010 Feb;21(2):295-302
19959710
Radiol Clin North Am. 1991 Mar;29(2):351-63
1998056
Birth Defects Res A Clin Mol Teratol. 2003 Aug;67(8):591-4
14632309
J Pediatr Urol. 2007 Feb;3(1):2-9
17476318
Br J Nutr. 2003 Jul;90(1):33-9
12844373
Am J Kidney Dis. 2006 Jun;47(6):1004-12
16731295
Am J Physiol Renal Physiol. 2007 Aug;293(2):F494-500
17494089
Dev Cell. 2004 May;6(5):709-17
15130495
J Am Soc Nephrol. 2008 May;19(5):891-903
18305125
Mol Cell. 1999 Jan;3(1):1-10
10024874
Cell Mol Life Sci. 2009 Jul;66(14):2249-61
19326048
Hum Mol Genet. 2006 Dec 1;15(23):3420-8
17047028
Pediatr Nephrol. 2009 Jun;24(6):1113-20
18958502
J Clin Invest. 2009 Apr;119(4):924-35
19273906
Dev Cell. 2005 Aug;9(2):283-92
16054034
J Pediatr Urol. 2009 Feb;5(1):47-52
18977697
Development. 1998 Sep;125(17):3313-22
9693135
Dev Cell. 2009 Aug;17(2):199-209
19686681
Physiol Genomics. 2000 Sep 08;3(3):121-31
11015607
Nat Genet. 1997 Feb;15(2):157-64
9020840
J Am Soc Nephrol. 2008 Apr;19(4):825-31
18235093
Am J Physiol Heart Circ Physiol. 2009 May;296(5):H1255-62
19252086
Development. 2001 Jun;128(11):2153-61
11493536
J Clin Invest. 1998 Oct 15;102(8):1489-97
9788961
Kidney Int. 1998 Dec;54(6):1832-42
9853247
J Am Soc Nephrol. 2010 May;21(5):803-10
20299358
Am J Physiol Renal Physiol. 2010 Mar;298(3):F807-17
20032120
Physiol Genomics. 2005 Jun 16;22(1):48-56
15827236
Development. 2010 Jan;137(2):347-57
20040500
Genome Res. 2003 Aug;13(8):1855-62
12902379
Kidney Int. 2008 Nov;74(10):1287-93
18650792
Pediatrics. 1965 Apr;35:601-19
14269712
Kidney Int. 1987 Nov;32(5):684-90
2828748
Development. 2001 Dec;128(23):4747-56
11731455
Am J Hypertens. 1988 Oct;1(4 Pt 1):335-47
3063284
Nat Genet. 2009 Jul;41(7):793-9
19543268
J Urol. 2005 Aug;174(2):713-7
16006956
Development. 1999 Mar;126(6):1139-48
10021334
J Am Soc Nephrol. 2010 Jan;21(1):113-23
19959718
Development. 2009 Mar;136(6):879-89
19234061
Semin Nephrol. 2009 Jul;29(4):321-37
19615554
Pediatr Nephrol. 1994 Oct;8(5):570-3
7819003
Nat Genet. 2005 Sep;37(9):964-8
16116425
Science. 1953 Jul 10;118(3054):52-5
13076182
Pediatr Nephrol. 1999 Apr;13(3):187-91
10353402
J Am Soc Nephrol. 2006 Aug;17(8):2253-63
16790508
Development. 2009 Dec;136(23):3863-74
19906853
Differentiation. 2006 Sep;74(7):402-21
16916378
J Clin Invest. 2006 Mar;116(3):663-74
16511601
Dev Biol. 2006 Nov 15;299(2):466-77
17022962
Nat Genet. 1996 Oct;14(2):171-3
8841187
J Clin Invest. 2000 Apr;105(7):863-73
10749566
J Clin Invest. 1995 Dec;96(6):2947-54
8675666
J Med Genet. 2006 Jan;43(1):84-90
15930087
J Am Soc Nephrol. 2007 Jun;18(6):1915-21
17513325
Eur J Med Genet. 2005 Apr-Jun;48(2):131-44
16053904
Cell Stem Cell. 2008 Aug 7;3(2):169-81
18682239
J Am Soc Nephrol. 2006 Apr;17(4):1005-14
16495379
J Urol. 2003 Nov;170(5):1722-6
14532762
J Am Soc Nephrol. 2003 Aug;14(8):2004-14
12874454
Nephrol Dial Transplant. 2006 Dec;21(12):3415-21
17012268
Pediatr Int. 2003 Oct;45(5):610-6
14521546
Pediatr Nephrol. 2010 Jun;25(6):1073-9
20155289
J Am Soc Nephrol. 2006 Oct;17(10):2864-70
16971658
J Am Soc Nephrol. 2007 May;18(5):1374-80
17429049
J Am Soc Nephrol. 2006 Feb;17(2):497-503
16371430
Dev Biol. 2007 Apr 15;304(2):701-12
17316599
Pediatrics. 1979 Jun;63(6):886-9
450525
Genes Dev. 2007 Sep 15;21(18):2358-70
17875669
Am J Kidney Dis. 2009 Feb;53(2):327-31
18950917
Pediatr Nephrol. 2009 Dec;24(12):2361-8
19685083
Dev Cell. 2007 Oct;13(4):580-92
17925232
Am J Perinatol. 1995 Nov;12(6):425-8
8579655
Bioessays. 2008 Jan;30(1):15-24
18081007
Kidney Int. 2005 Apr;67(4):1256-67
15780078
Pediatr Nephrol. 2005 Nov;20(11):1541-4
16133060
Kidney Int. 2009 Jun;75(11):1153-1165
19340092
J Urol. 2001 Nov;166(5):1848-52
11586245
J Am Soc Nephrol. 2008 Apr;19(4):667-71
18287559
Am J Med Genet. 1987 Apr;26(4):863-72
3591828
Pediatr Nephrol. 2008 Oct;23(10):1769-77
18607644
Mamm Genome. 2009 Mar;20(3):140-51
19169742
Nature. 1994 Jan 27;367(6461):380-3
8114940