Top

Published in:

01-03-2011 | Review

Genetics of congenital anomalies of the kidney and urinary tract

Authors: Renfang Song, Ihor V. Yosypiv

Published in: Pediatric Nephrology | Issue 3/2011

Abstract

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.

Available only for authorised users

Daneman A, Alton DJ (1991) Radiographic manifestations of renal anomalies. Radiol Clin North Am 29:351–363PubMed

Nakanishi K, Yoshikawa N (2003) Genetic disorders of human congenital anomalies of the kidney and urinary tract (CAKUT). Pediatr Int 45:610–616PubMed

North American Pediatric Renal Trials and Collaborative Studies (2008) NAPRTCS Annual report. Available at https://web.emmes.com/study/ped/annlrept/Annual%20Report%20-2008.pdf

Baluarte HJ, Gruskin AB, Ingelfinger JR, Stablein D, Tejani A (1994) Analysis of hypertension in children post renal transplantation: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Nephrol 8:570–573PubMed

Saxen L (1987) Organogenesis of the kidney. Cambridge University Press, Cambridge

Costantini F (2006) Renal branching morphogenesis: concepts, questions, and recent advances. Differentiation 74:402–421PubMed

Dressler GR (2009) Advances in early kidney specification, development and patterning. Development 136:3863–3874PubMed

Reidy KJ, Rosenblum ND (2009) Cell and molecular biology of kidney development. Semin Nephrol 29:321–337PubMed

Yosypiv IV (2009) Renin-angiotensin system-growth factor cross-talk: a novel mechanism for ureteric bud morphogenesis. Pediatr Nephrol 24:1113–1120PubMed

10.

Grobstein C (1953) Inductive epithelio-mesenchymal interaction in cultured organ rudiments of the mouse metanephros. Science 118:52–55PubMed

11.

Ekblom P (1989) Developmentally regulated conversion of mesenchyme to epithelium. FASEB J 3:2141–2150PubMed

12.

al-Awqati Q, Goldberg MR (1998) Architectural patterns in branching morphogenesis in the kidney. Kidney Int 54:1832–1842PubMed

13.

Fetterman GH, Shuplock NA, Rhilipp FJ, Gregg HS (1965) The growth and maturation of human glomeruli and proximal convolutions from term to adulthood: studies by microdissection. Pediatrics 35:601–619PubMed

14.

Mendelsohn C (2009) Using mouse models to understand normal and abnormal urogenital tract development. Organogenesis 5:306–314PubMed

15.

Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V (1994) Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor. Nature Ret 367:380–383

16.

Chi X, Michos O, Shakya R, Riccio P, Enomoto H, Licht JD, Asai N, Takahashi M, Ohgami N, Kato M, Mendelsohn C, Costantini F (2009) Ret-dependent cell rearrangements in the Wolffian duct epithelium initiate ureteric bud morphogenesis. Dev Cell 17:199–209PubMed

17.

Moreau E, Vilar J, Lelièvre-Pégorier M, Merlet-Bénichou C, Gilbert T (1998) Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control. Am J Physiol 275:F938–F945PubMed

18.

Basson MA, Watson-Johnson J, Shakya R, Akbulut S, Hyink D, Costantini FD, Wilson PD, Mason IJ, Licht JD (2006) Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 299:466–477PubMed

19.

Clarke JC, Patel SR, Raymond RM Jr, Andrew S, Robinson BG, Dressler GR, Brophy PD (2006) Regulation of c-Ret in the developing kidney is responsive to Pax2 gene dosage. Hum Mol Genet 15:3420–3428PubMed

20.

Michos O, Cebrian C, Hyink D, Grieshammer U, Williams L, D'Agati V, Licht JD, Martin GR, Costantini F (2010) Kidney development in the absence of Gdnf and Spry1 requires Fgf10. PLoS Genet 6:1–11

21.

Hatini A, Huh SO, Herzlinger D, Soares VC, Lai E (1996) Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev 10:1467–1478PubMed

22.

Mendelsohn C, Batourina E, Fung S, Gilbert T, Dodd J (1999) Stromal cells mediate retinoid-dependent functions essential for renal development. Development 126:1139–1148PubMed

23.

Cullen-McEwen LA, Caruana G, Bertram JF (2005) The where, what and why of the developing renal stroma. Nephron Exp Nephrol 99:e1–e8PubMed

24.

Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372:679–683PubMed

25.

Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9:283–392PubMed

26.

Iglesias DM, Hueber PA, Chu L, Campbell R, Patenaude AM, Dziarmaga AJ, Quinlan J, Mohamed O, Dufort D, Goodyer PR (2007) Canonical WNT signaling during kidney development. Am J Physiol 293:F494–F500

27.

Lokmane L, Heliot C, Garcia-Villalba P, Fabre M, Cereghini S (2010) vHNF1 functions in distinct regulatory circuits to control ureteric bud branching and early nephrogenesis. Development 137:347–357PubMed

28.

Karner CM, Chirumamilla R, Aoki S, Igarashi P, Wallingford JB, Carroll TJ (2009) Wnt9b signaling regulates planar cell polarity and kidney tubule morphogenesis. Nat Genet 41:793–799PubMed

29.

Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, McMahon AP (2008) Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3:169–181PubMed

30.

Reggiani L, Raciti D, Airik R, Kispert A, Brändli AW (2007) The prepattern transcription factor Irx3 directs nephron segment identity. Genes Dev 21:2358–2370PubMed

31.

Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, McMahon AP, Kopan R (2007) Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development 134:801–811PubMed

32.

Fujimura S, Jiang Q, Kobayashi C, Nishinakamura R (2010) Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol 21:803–810PubMed

33.

Ryan G, Steele-Perkins V, Morris JF, Rauscher FJ 3rd, Dressler GR (1995) Repression of Pax-2 by WT1 during normal kidney development. Development 121:867–875PubMed

34.

Suleiman H, Heudobler D, Raschta AS, Zhao Y, Zhao Q, Hertting I, Vitzthum H, Moeller MJ, Holzman LB, Rachel R, Johnson R, Westphal H, Rascle A, Witzgall R (2007) The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes. Dev Biol 304:701–712PubMed

35.

Reidy KJ, Villegas G, Teichman J, Veron D, Shen W, Jimenez J, Thomas D, Tufro A (2009) Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development 136:3979–3989PubMed

36.

Tufro A, Norwood VF, Carey RM, Gomez RA (1999) Vascular endothelial growth factor induces nephrogenesis and vasculogenesis. J Am Soc Nephrol 10:2125–2134PubMed

37.

Lindahl P, Hellström M, Kalén M, Karlsson L, Pekny M, Pekna M, Soriano P, Betsholtz C (1998) Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli. Development 125:3313–3322PubMed

38.

Batourina E, Choi C, Paragas N, Bello N, Hensle T, Costantini FD, Schuchardt A, Bacallao RL, Mendelsohn CL (2002) Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret. Nat Genet 32:109–115PubMed

39.

Batourina E, Tsai S, Lambert S, Sprenkle P, Viana R, Dutta S, Hensle T, Wang F, Niederreither K, McMahon AP, Carroll TJ, Mendelsohn CL (2005) Apoptosis induced by vitamin A signaling is crucial for connecting the ureters to the bladder. Nat Genet 37:1082–1089PubMed

40.

Uetani N, Bertozzi K, Chagnon MJ, Hendriks W, Tremblay ML, Bouchard M (2009) Maturation of ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases. J Clin Invest 119:924–935PubMed

41.

Hiraoka M, Hori C, Tsukahara H, Kasuga K, Ishihara Y, Sudo M (1997) Congenitally small kidneys with reflux as a common cause of nephropathy in boys. Kidney Int 52:811–816PubMed

42.

Wiesel A, Queisser-Luft A, Clementi M, Bianca S, Stoll C (2005) Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709, 030 births in 12 European countries. Eur J Med Genet 48:131–144PubMed

43.

Miyazaki Y, Oshima K, Fogo A, Hogan BL, Ichikawa I (2000) Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter. J Clin Invest 105:863–873PubMed

44.

Grieshammer U, Ma L, Plump AS, Wang F, Tessier-Lavigne M, Martin GR (2004) SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 6:709–717PubMed

45.

Garne E, Loane M, Wellesley D, Barisic I (2009) Congenital hydronephrosis: prenatal diagnosis and epidemiology in Europe. J Pediatr Urol 5:47–52PubMed

46.

Airik R, Bussen M, Singh MK, Petry M, Kispert A (2006) Tbx18 regulates the development of the ureteral mesenchyme. J Clin Invest 116:663–674PubMed

47.

Nie X, Sun J, Gordon RE, Cai CL, Xu PX (2010) SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation. Development 137:755–765PubMed

48.

Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens 1:335–347PubMed

49.

Lisle SJ, Lewis RM, Petry CJ, Ozanne SE, Hales CN, Forhead AJ (2003) Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring. Br J Nutr 90:33–39PubMed

50.

Weizer AZ, Silverstein AD, Auge BK, Delvecchio FC, Raj G, Albala DM, Leder R, Preminger GM (2003) Determining the incidence of horseshoe kidney from radiographic data at a single institution. J Urol 170:1722–1726PubMed

51.

Levinson RS, Batourina E, Choi C, Vorontchikhina M, Kitajewski J, Mendelsohn CL (2005) Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development. Development 132:529–539PubMed

52.

Hatada I, Ohashi H, Fukushima Y, Kaneko Y, Inoue M, Komoto Y, Okada A, Ohishi S, Nabetani A, Morisaki H, Nakayama M, Niikawa N, Mukai T (1996) An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome. Nat Genet 14:171–173PubMed

53.

Nishio S, Tian X, Gallagher AR, Yu Z, Patel V, Igarashi P, Somlo S (2010) Loss of oriented cell division does not initiate cyst formation. J Am Soc Nephrol 21:295–302PubMed

54.

McMahon AP, Aronow BJ, Davidson DR, Davies JA, Gaido KW, Grimmond S, Lessard JL, Little MH, Potter SS, Wilder EL, Zhang P (2008) GUDMAP: the genitourinary developmental molecular anatomy project. J Am Soc Nephrol 19:667–671PubMed

55.

Rosenblum ND (2008) Developmental biology of the human kidney. Semin Fetal Neonatal Med 13:125–132PubMed

56.

Rossetti S, Harris PC (2007) Genotype-phenotype correlations in autosomal dominant and autosomal recessive polycystic kidney disease. J Am Soc Nephrol 18:1374–1380PubMed

57.

Abdelhak S, Kalatzis V, Heilig R, Compain S, Samson D, Vincent C, Weil D, Cruaud C, Sahly I, Leibovici M, Bitner-Glindzicz M, Francis M, Lacombe D, Vigneron J, Charachon R, Boven K, Bedbeder P, Van Regemorter N, Weissenbach J, Petit C (1997) A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family. Nat Genet 15:157–164PubMed

58.

Gresh L, Fischer E, Reimann A, Tanguy M, Garbay S, Shao X, Hiesberger T, Fiette L, Igarashi P, Yaniv M, Pontoglio M (2004) A transcriptional network in polycystic kidney disease. EMBO J 23:1657–1668PubMed

59.

Mache CJ, Preisegger KH, Kopp S, Ratschek M, Ring E (2002) De novo HNF-1 beta gene mutation in familial hypoplastic glomerulocystic kidney disease. Pediatr Nephrol 17:1021–1026PubMed

60.

Edghill EL, Bingham C, Ellard S, Hattersley AT (2005) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84–90PubMed

61.

Ulinski T, Lescure S, Beaufils S, Guigonis V, Decramer S, Morin D, Clauin S, Deschênes G, Bouissou F, Bensman A, Bellanné-Chantelot C (2006) Renal phenotypes related to hepatocyte nuclear factor-1beta (TCF2) mutations in a pediatric cohort. J Am Soc Nephrol 17:497–503PubMed

62.

Nakayama M, Nozu K, Goto Y, Kamei K, Ito S, Sato H, Emi M, Nakanishi K, Tsuchiya S, Iijima K (2010) HNF1B alterations associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol 25:1073–1079PubMed

63.

Hart TC, Gorry MC, Hart PS, Woodard AS, Shihabi Z, Sandhu J, Shirts B, Xu L, Zhu H, Barmada MM, Bleyer AJ (2002) Mutations of the UMOD gene are responsible for medullary cystic kidney disease 2 and familial juvenile hyperuricaemic nephropathy. J Med Genet 39:882–892PubMed

64.

Wolf MT, Hoskins BE, Beck BB, Hoppe B, Tasic V, Otto EA, Hildebrandt F (2009) Mutation analysis of the Uromodulin gene in 96 individuals with urinary tract anomalies (CAKUT). Pediatr Nephrol 24:55–60PubMed

65.

Benetti E, Caridi G, Vella MD, Rampoldi L, Ghiggeri GM, Artifoni L, Murer L (2009) Immature renal structures associated with a novel UMOD sequence variant. Am J Kidney Dis 53:327–331PubMed

66.

Quinlan J, Lemire M, Hudson T, Qu H, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Zhang Z, Houghton F, Goodyer P (2007) A common variant of the PAX2 gene is associated with reduced newborn kidney size. J Am Soc Nephrol 18:1915–1921PubMed

67.

Zhang Z, Quinlan J, Grote D, Lemire M, Hudson T, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Houghton F, Bouchard M, Goodyer P (2009) Common variants of the glial cell-derived neurotrophic factor gene do not influence kidney size of the healthy newborn. Pediatr Nephrol 24:1151–1157PubMed

68.

Brophy PD, Ostrom L, Lang KM, Dressler GR (2001) Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene. Development 128:4747–4756PubMed

69.

Weber S, Moriniere V, Knüppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiené A, Mir S, Montini G, Peco-Antic A, Wühl E, Zurowska AM, Mehls O, Antignac C, Schaefer F, Salomon R (2006) Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol 17:2864–2870PubMed

70.

Cordell HJ, Darlay R, Charoen P, Stewart A, Gullett AM, Lambert HJ, Malcolm S, Feather SA, Goodship TH, Woolf AS, Kenda RB, Goodship JA (2010) Whole-genome linkage and association scan in primary, nonsyndromic vesicoureteric reflux. J Am Soc Nephrol 21:113–123PubMed

71.

Bertoli-Avella AM, Conte ML, Punzo F, de Graaf BM, Lama G, La Manna A, Polito C, Grassia C, Nobili B, Rambaldi PF, Oostra BA, Perrotta S (2008) ROBO2 gene variants are associated with familial vesicoureteral reflux. J Am Soc Nephrol 19:825–831PubMed

72.

Zu S, Bartik Z, Zhao S, Sillen U, Nordenskjöld A (2009) Mutations in the ROBO2 and SLIT2 genes are rare causes of familial vesico-ureteral reflux. Pediatr Nephrol 24:1501–1508PubMed

73.

Patterson LT, Pembaur M, Potter SS (2001) Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Development 128:2153–2161PubMed

74.

Bouba I, Siomou E, Stefanidis CJ, Emmanouilidou A, Galidi A, Hatzi E, Markoula S, Mitsioni A, Siamopoulou A, Georgiou I (2009) Absence of mutations in the HOXA11 and HOXD11 genes in children with congenital renal malformations. Pediatr Nephrol 24:1569–1572PubMed

75.

Wu XR, Kong XP, Pellicer A, Kreibich G, Sun TT (2009) Uroplakins in urothelial biology, function, and disease. Kidney Int 75:1153–1165PubMed

76.

Jenkins D, Bitner-Glindzicz M, Malcolm S, Allison J, de Bruyn R, Flanagan S, Thomas DF, Belk RA, Feather SA, Bingham C, Southgate J, Woolf AS (2006) Mutation analyses of Uroplakin II in children with renal tract malformations. Nephrol Dial Transplant 21:3415–3421PubMed

77.

Jenkins D, Bitner-Glindzicz M, Thomasson L, Malcolm S, Warne SA, Feather SA, Flanagan SE, Ellard S, Bingham C, Santos L, Henkemeyer M, Zinn A, Baker LA, Wilcox DT, Woolf AS (2007) Mutational analyses of UPIIIA, SHH, EFNB2 and HNF1beta in persistent cloaca and associated kidney malformations. J Pediatr Urol 3:2–9PubMed

78.

Schönfelder EM, Knüppel T, Tasic V, Miljkovic P, Konrad M, Wühl E, Antignac C, Bakkaloglu A, Schaefer F, Weber S (2006) Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans. Am J Kidney Dis 47:1004–1012PubMed

79.

Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knüppel T, Zurowska AM, Caldas-Alfonso A, Litwin M, Emre S, Ghiggeri GM, Bakkaloglu A, Mehls O, Antignac C, Network E, Schaefer F, Burdine RD (2008) SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol 19:891–903PubMed

80.

Tabatabaeifar M, Schlingmann KP, Litwin M, Emre S, Bakkaloglu A, Mehls O, Antignac C, Schaefer F, Weber S (2009) Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatr Nephrol 24:2361–2368PubMed

81.

Lo HS, Wang Z, Hu Y, Yang HH, Gere S, Buetow KH, Lee MP (2003) Allelic variation in gene expression is common in the human genome. Genome Res 13:1855–1862PubMed

82.

Marini M, Giacopelli F, Seri M, Ravazzolo R (2005) Interaction of the LMX1B and PAX2 gene products suggests possible molecular basis of differential phenotypes in Nail-Patella syndrome. Eur J Hum Genet 13:789–792PubMed

83.

Fain PR, McFann KK, Taylor MR, Tison M, Johnson AM, Reed B, Schrier RW (2005) Modifier genes play a significant role in the phenotypic expression of PKD1. Kidney Int 67:1256–1267PubMed

84.

Patel SR, Kim D, Levitan I, Dressler GR (2007) The BRCT-domain containing protein PTIP links PAX2 to a histone H3, lysine 4 methyltransferase complex. Dev Cell 13:580–592PubMed

85.

Pogribny IP, Beland FA (2009) DNA hypomethylation in the origin and pathogenesis of human diseases. Cell Mol Life Sci 66:2249–2261PubMed

86.

Gomez RA, Pentz ES, Jin X, Cordaillat M, Sequeira Lopez ML (2009) CBP and p300 are essential for renin cell identity and morphological integrity of the kidney. Am J Physiol 296:H1255–H1262

87.

Welham SJ, Riley PR, Wade A, Hubank M, Woolf AS (2005) Maternal diet programs embryonic kidney gene expression. Physiol Genomics 22:48–56PubMed

88.

El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, Meleg-Smith S (2000) Bradykinin B2 null mice are prone to renal dysplasia: gene-environment interactions in kidney development. Physiol Genomics 3:121–131PubMed

89.

Furu L, Onuchic LF, Gharavi A, Hou X, Esquivel EL, Nagasawa Y, Bergmann C, Senderek J, Avner E, Zerres K, Germino GG, Guay-Woodford LM, Somlo S (2003) Milder presentation of recessive polycystic kidney disease requires presence of amino acid substitution mutations. J Am Soc Nephrol 14:2004–2014PubMed

90.

McPherson E, Carey J, Kramer A, Hall JG, Pauli RM, Schimke RN, Tasin MH (1987) Dominantly inherited renal adysplasia. Am J Med Genet 26:863–872PubMed

91.

Tory K, Lacoste T, Burglen L, Morinière V, Boddaert N, Macher MA, Llanas B, Nivet H, Bensman A, Niaudet P, Antignac C, Salomon R, Saunier S (2007) High NPHP1 and NPHP6 mutation rate in patients with Joubert syndrome and nephronophthisis: potential epistatic effect of NPHP6 and AHI1 mutations in patients with NPHP1 mutations. J Am Soc Nephrol 18:1566–1575PubMed

92.

Battin M, Albersheim S, Newman D (1995) Congenital genitourinary tract abnormalities following cocaine exposure in utero. Am J Perinatol 12:425–428PubMed

93.

Qazi Q, Masakawa A, Milman D, McGann B, Chua A, Haller J (1979) Renal anomalies in fetal alcohol syndrome. Pediatrics 63:886–889PubMed

94.

Smith CL (2008) A shifting paradigm: histone deacetylases and transcriptional activation. Bioessays 30:15–24PubMed

95.

Nottke A, Colaiácovo MP, Shi Y (2009) Developmental roles of the histone lysine demethylases. Development 136:879–889PubMed

96.

Pastorelli LM, Wells S, Fray M, Smith A, Hough T, Harfe BD, McManus MT, Smith L, Woolf AS, Cheeseman M, Greenfield A (2009) Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract. Mamm Genome 20:140–151PubMed

97.

Oshima K, Miyazaki Y, Brock JW, Adams MC, Ichikawa I, Pope JC (2001) Angiotensin type II receptor expression and ureteral budding. J Urol 166:1848–1852PubMed

98.

Nishimura H, Yerkes E, Hohenfellner K, Miyazaki Y, Ma J, Hunley TE, Yoshida H, Ichiki T, Threadgill D, Phillips JA 3rd, Hogan BM, Fogo A, Brock JW 3rd, Inagami T, Ichikawa I (1999) Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell 3:1–10PubMed

99.

Miyazaki Y, Tsuchida S, Nishimura H, Pope JC 4th, Harris RC, McKanna JM, Inagami T, Hogan BL, Fogo A, Ichikawa I (1998) Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 102:1489–1497PubMed

100.

Chen YW, Tran S, Chenier I, Chan JS, Ingelfinger JR, Inagami T, Zhang SL (2008) Deficiency of intrarenal angiotensin II type 2 receptor impairs paired homeo box-2 and N-myc expression during nephrogenesis. Pediatr Nephrol 23:1769–1777PubMed

101.

Yosypiv IV, Boh MK, Spera M, El-Dahr SS (2008) Downregulation of Spry-1, an inhibitor of GDNF/Ret, as a mechanism for angiotensin II-induced ureteric bud branching. Kidney Int 74:1287–1293PubMed

102.

Song R, Spera M, Garrett C, Yosypiv IV (2010) Angiotensin II-induced activation of c-Ret signaling is critical in ureteric bud branching morphogenesis. Mech Dev 127:21–27PubMed

103.

Yosypiv IV, Schroeder M, El-Dahr SS (2006) AT1R-EGFR crosstalk regulates ureteric bud branching morphogenesis. J Am Soc Nephrol 17:1005–1014PubMed

104.

Song R, Spera M, Garrett C, El-Dahr S, Yosypiv IV (2010) Angiotensin II AT₂ Receptor Regulates Ureteric Bud Morphogenesis. Am J Physiol 298:F807–F817

105.

Niimura F, Labosky PA, Kakuchi J, Okubo S, Yoshida H, Oikawa T, Ichiki T, Naftilan AJ, Fogo A, Inagami T (1995) Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation. J Clin Invest 96:2947–2954PubMed

106.

Sequeira-Lopez ML, Weatherford ET, Borges GR, Monteagudo MC, Pentz ES, Harfe BD, Carretero O, Sigmund CD, Gomez RA (2010) The microRNA-processing enzyme dicer maintains juxtaglomerular cells. J Am Soc Nephrol 21:460–467PubMed

107.

Schütz S, Le Moullec JM, Corvol P, Gasc JM (1996) Early expression of all the components of the renin-angiotensin-system in human development. Am J Pathol 149:2067–2079PubMed

108.

Mounier F, Hinglais N, Sich M, Gros F, Lacoste M, Deris Y, Alhenc-Gelas F, Gubler MC (1987) Ontogenesis of angiotensin-I converting enzyme in human kidney. Kidney Int 32:684–690PubMed

109.

Schaefer C (2003) Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity. Birth Defects Res A Clin Mol Teratol 67:591–594PubMed

110.

Tabacova S, Little R, Tsong Y, Vega A, Kimmel CA (2003) Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment. Pharmacoepidemiol Drug Saf 12:633–646PubMed

111.

Gribouval O, Gonzales M, Neuhaus T (2005) Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet 37:964–968PubMed

112.

Lacoste M, Cai Y, Guicharnaud L, Mounier F, Dumez Y, Bouvier R, Dijoud F, Gonzales M, Chatten J, Delezoide AL, Daniel L, Joubert M, Laurent N, Aziza J, Sellami T, Amar HB, Jarnet C, Frances AM, Daïkha-Dahmane F, Coulomb A, Neuhaus TJ, Foliguet B, Chenal P, Marcorelles P, Gasc JM, Corvol P, Gubler MC (2006) Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: role of the renin-angiotensin system. J Am Soc Nephrol 17:2253–2263PubMed

113.

Hohenfellner K, Hunley TE, Schloemer C, Brenner W, Yerkes E, Zepp F, Brock JW 3rd, Kon V (1999) Angiotensin type 2 receptor is important in the normal development of the ureter. Pediatr Nephrol 13:187–191PubMed

114.

Hahn H, Ku SE, Kim KS, Park YS, Yoon CH, Cheong HI (2005) Implication of genetic variations in congenital obstructive nephropathy. Pediatr Nephrol 20:1541–1544PubMed

115.

Rigoli L, Chimenz R, di Bella C, Cavallaro E, Caruso R, Briuglia S, Fede C, Salpietro CD (2004) Angiotensin-converting enzyme and angiotensin type 2 receptor gene genotype distributions in Italian children with congenital uropathies. Pediatr Res 56:988–993PubMed

116.

Stanković A, Zivković M, Kostić M, Atanacković J, Krstić Z, Alavantić D (2010) Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT. Clin Biochem 43:71–75PubMed

117.

Peruzzi L, Lombardo F, Amore A, Merlini E, Restagno G, Silvestro L, Papalia T, Coppo R (2005) Low renin-angiotensin system activity gene polymorphism and dysplasia associated with posterior urethral valves. J Urol 174:713–717PubMed

118.

Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ (2008) Renal aplasia in humans is associated with RET mutations. Am J Hum Genet 82:344–351PubMed

119.

Wolf MT, Beck BB, Zaucke F, Kunze A, Misselwitz J, Ruley J, Ronda T, Fischer A, Eifinger F, Licht C, Otto E, Hoppe B, Hildebrandt F (2007) The Uromodulin C744G mutation causes MCKD2 and FJHN in children and adults and may be due to a possible founder effect. Kidney Int 71:574–581PubMed

120.

O'Toole JF, Liu Y, Davis EE, Westlake CJ, Attanasio M, Otto EA, Seelow D, Nurnberg G, Becker C, Nuutinen M, Kärppä M, Ignatius J, Uusimaa J, Pakanen S, Jaakkola E, van den Heuvel LP, Fehrenbach H, Wiggins R, Goyal M, Zhou W, Wolf MT, Wise E, Helou J, Allen SJ, Murga-Zamalloa CA, Ashraf S, Chaki M, Heeringa S, Chernin G, Hoskins BE, Chaib H, Gleeson J, Kusakabe T, Suzuki T, Isaac RE, Quarmby LM, Tennant B, Fujioka H, Tuominen H, Hassinen I, Lohi H, van Houten JL, Rotig A, Sayer JA, Rolinski B, Freisinger P, Madhavan SM, Herzer M, Madignier F, Prokisch H, Nurnberg P, Jackson P, Khanna H, Katsanis N, Hildebrandt F (2010) Individuals with mutations in XPNPEP3, which encodes a mitochondrial protein, develop a nephronophthisis-like nephropathy. J Clin Invest 120:791–802PubMed

121.

Nakano T, Niimura F, Hohenfellner K, Miyakita E, Ichikawa I (2003) Screening for mutations in BMP4 and FOXC1 genes in congenital anomalies of the kidney and urinary tract in humans. Tokai J Exp Clin Med 28:121–126PubMed

Title: Genetics of congenital anomalies of the kidney and urinary tract
Authors: Renfang Song
Ihor V. Yosypiv
Publication date: 01-03-2011
Publisher: Springer-Verlag
Published in: Pediatric Nephrology / Issue 3/2011
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-010-1629-4

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Genetics of congenital anomalies of the kidney and urinary tract

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2011

Markers of childhood lupus nephritis indicating disease activity

Four family cases of acute renal failure: answer

Four family cases of acute renal failure: question

The genetic components of idiopathic nephrolithiasis

Membranoproliferative glomerulonephritis with C3NeF and genetic complement dysregulation

Expression and function of the Ets transcription factor pea3 during formation of zebrafish pronephros