Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans

Pediatric Nephrology

Volumn 29, Issue 4, 2014, Pages 695-704

  Vivante, Asaf ^a,b   Kohl, Stefan ^a   Hwang, Daw Yang ^a   Dworschak, Gabriel C ^a   Hildebrandt, Friedhelm ^a,c  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b SHEBA MEDICAL CENTER   (Israel)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

CAKUT; Congenital Anomalies of the Kidney and Urinary Tract; Genetic kidney disease; Monogenic disease

Indexed keywords

BONE MORPHOGENETIC PROTEIN 4; HEPATOCYTE NUCLEAR FACTOR 1BETA; MUCIN 1; PROTEIN RET; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR GATA 3; TRANSCRIPTION FACTOR SIX1; TRANSCRIPTION FACTOR SIX2; TRANSCRIPTION FACTOR SIX5; TRANSCRIPTION FACTOR SOX17; UNCLASSIFIED DRUG; VELAFERMIN; WNT4 PROTEIN;

ACE GENE; AGT GENE; AGTR1 GENE; BRANCHING MORPHOGENESIS; CAKUT; CHD1L GENE; CHILDHOOD DISEASE; CHRONIC KIDNEY DISEASE; CONFERENCE PAPER; DEVELOPMENTAL GENE; DSTYK GENE; EPITHELIAL MESENCHYMAL TRANSITION; EYA1 GENE; FRAS1 GENE; FREM2 GENE; GENE; GENE MUTATION; GENETIC REGULATION; HIGH THROUGHPUT SEQUENCING; HUMAN; KAL1 GENE; KIDNEY DEVELOPMENT; KIDNEY MALFORMATION; NONHUMAN; PRIORITY JOURNAL; REN GENE; ROBO2 GENE; SALL1 GENE; TNXB GENE; TRAP1 GENE; UMOD GENE; UPK3A GENE;

ANIMALS; HUMANS; KIDNEY; KIDNEY DISEASES; UROGENITAL ABNORMALITIES;

EID: 84896696202     PISSN: 0931041X     EISSN: 1432198X     Source Type: Journal    
DOI: 10.1007/s00467-013-2684-4     Document Type: Conference Paper

References (75)

1. Schedl A (2007) Renal abnormalities and their developmental origin. Nat Rev Genet 8:791-802
2. (2008) North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (2008) 2008 Annual report. The EMMES Corporation, Rockville, MD
3. Sanyanusin P, Schimmenti LA, McNoe LA, Ward TA, Pierpont ME, Sullivan MJ, Dobyns WB, Eccles MR (1995) Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux. Nat Genet 9:358-364
4. Lindner TH, Njolstad PR, Horikawa Y, Bostad L, Bell GI, Sovik O (1999) A novel syndrome of diabetes mellitus, renal dysfunction and genital malformation associated with a partial deletion of the pseudo-POU domain of hepatocyte nuclear factor-1beta. Hum Mol Genet 8:2001-2008
5. 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 15:157-164
6. Bulum B, Ozcakar ZB, Ustuner E, Dusunceli E, Kavaz A, Duman D, Walz K, Fitoz S, Tekin M, Yalcinkaya F (2013) High frequency of kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT. Pediatr Nephrol 28:2143-2147
7. Yosypiv IV (2012) Congenital anomalies of the kidney and urinary tract: a genetic disorder? Int J Nephrol. doi: 10.1155/2012/909083
8. Chen F (2009) Genetic and developmental basis for urinary tract obstruction. Pediatr Nephrol 24:1621-1632
9. Renkema KY, Winyard PJ, Skovorodkin IN, Levtchenko E, Hindryckx A, Jeanpierre C, Weber S, Salomon R, Antignac C, Vainio S, Schedl A, Schaefer F, Knoers NV, Bongers EM (2011) Novel perspectives for investigating congenital anomalies of the kidney and urinary tract (CAKUT). Nephrol Dial Transplant 26:3843-3851
10. Sanna-Cherchi S, Caridi G, Weng PL, Scolari F, Perfumo F, Gharavi AG, Ghiggeri GM (2007) Genetic approaches to human renal agenesis/hypoplasia and dysplasia. Pediatr Nephrol 22:1675-1684
11. Weber S (2012) Novel genetic aspects of congenital anomalies of kidney and urinary tract. Curr Opin Pediatr 24:212-218
12. Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knuppel 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 19:891-903
13. Pandolfi PP, Roth ME, Karis A, Leonard MW, Dzierzak E, Grosveld FG, Engel JD, Lindenbaum MH (1995) Targeted disruption of the GATA3 gene causes severe abnormalities in the nervous system and in fetal liver haematopoiesis. Nat Genet 11:40-44
14. Van Esch H, Groenen P, Nesbit MA, Schuffenhauer S, Lichtner P, Vanderlinden G, Harding B, Beetz R, Bilous RW, Holdaway I, Shaw NJ, Fryns JP, Van de Ven W, Thakker RV, Devriendt K (2000) GATA3 haplo-insufficiency causes human HDR syndrome. Nature 406:419-422
15. Horikawa Y, Iwasaki N, Hara M, Furuta H, Hinokio Y, Cockburn BN, Lindner T, Yamagata K, Ogata M, Tomonaga O, Kuroki H, Kasahara T, Iwamoto Y, Bell GI (1997) Mutation in hepatocyte nuclear factor-1 beta gene (TCF2) associated with MODY. Nat Genet 17:384-385
16. Hardelin JP, Levilliers J, del Castillo I, Cohen-Salmon M, Legouis R, Blanchard S, Compain S, Bouloux P, Kirk J, Moraine C, Chaussain JL, Weissenbach J, Petit C (1992) X chromosome-linked Kallmann syndrome: stop mutations validate the candidate gene. Proc Natl Acad Sci USA 89:8190-8194
17. Bower M, Salomon R, Allanson J, Antignac C, Benedicenti F, Benetti E, Binenbaum G, Jensen UB, Cochat P, DeCramer S, Dixon J, Drouin R, Falk MJ, Feret H, Gise R, Hunter A, Johnson K, Kumar R, Lavocat MP, Martin L, Moriniere V, Mowat D, Murer L, Nguyen HT, Peretz-Amit G, Pierce E, Place E, Rodig N, Salerno A, Sastry S, Sato T, Sayer JA, Schaafsma GC, Shoemaker L, Stockton DW, Tan WH, Tenconi R, Vanhille P, Vats A, Wang X, Warman B, Weleber RG, White SM, Wilson-Brackett C, Zand DJ, Eccles M, Schimmenti LA, Heidet L (2012) Update of PAX2 mutations in renal coloboma syndrome and establishment of a locus-specific database. Hum Mutat 33:457-466
18. Skinner MA, Safford SD, Reeves JG, Jackson ME, Freemerman AJ (2008) Renal aplasia in humans is associated with RET mutations. Am J Hum Genet 82:344-351
19. Yang Y, Houle AM, Letendre J, Richter A (2008) RET Gly691Ser mutation is associated with primary vesicoureteral reflux in the French-Canadian population from Quebec. Hum Mutat 29:695-702
20. Lu W, van Eerde AM, Fan X, Quintero-Rivera F, Kulkarni S, Ferguson H, Kim HG, Fan Y, Xi Q, Li QG, Sanlaville D, Andrews W, Sundaresan V, Bi W, Yan J, Giltay JC, Wijmenga C, de Jong TP, Feather SA, Woolf AS, Rao Y, Lupski JR, Eccles MR, Quade BJ, Gusella JF, Morton CC, Maas RL (2007) Disruption of ROBO2 is associated with urinary tract anomalies and confers risk of vesicoureteral reflux. Am J Hum Genet 80:616-632
21. Kohlhase J, Wischermann A, Reichenbach H, Froster U, Engel W (1998) Mutations in the SALL1 putative transcription factor gene cause Townes-Brocks syndrome. Nat Genet 18:81-83
22. Ruf RG, Xu PX, Silvius D, Otto EA, Beekmann F, Muerb UT, Kumar S, Neuhaus TJ, Kemper MJ, Raymond RM Jr, Brophy PD, Berkman J, Gattas M, Hyland V, Ruf EM, Schwartz C, Chang EH, Smith RJ, Stratakis CA, Weil D, Petit C, Hildebrandt F (2004) SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc Natl Acad Sci USA 101:8090-8095
23. Hoskins BE, Cramer CH, Silvius D, Zou D, Raymond RM, Orten DJ, Kimberling WJ, Smith RJ, Weil D, Petit C, Otto EA, Xu PX, Hildebrandt F (2007) Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am J Hum Genet 80:800-804
24. Gimelli S, Caridi G, Beri S, McCracken K, Bocciardi R, Zordan P, Dagnino M, Fiorio P, Murer L, Benetti E, Zuffardi O, Giorda R, Wells JM, Gimelli G, Ghiggeri GM (2010) Mutations in SOX17 are associated with congenital anomalies of the kidney and the urinary tract. Hum Mutat 31:1352-1359
25. Gbadegesin RA, Brophy PD, Adeyemo A, Hall G, Gupta IR, Hains D, Bartkowiak B, Rabinovich CE, Chandrasekharappa S, Homstad A, Westreich K, Wu G, Liu Y, Holanda D, Clarke J, Lavin P, Selim A, Miller S, Wiener JS, Ross SS, Foreman J, Rotimi C, Winn MP (2013) TNXB Mutations Can Cause Vesicoureteral Reflux. J Am Soc Nephrol 24:1313-1322
26. Jenkins D, Bitner-Glindzicz M, Malcolm S, Hu CC, Allison J, Winyard PJ, Gullett AM, Thomas DF, Belk RA, Feather SA, Sun TT, Woolf AS (2005) De novo Uroplakin IIIa heterozygous mutations cause human renal adysplasia leading to severe kidney failure. J Am Soc Nephrol 16:2141-2149
27. Self M, Lagutin OV, Bowling B, Hendrix J, Cai Y, Dressler GR, Oliver G (2006) Six2 is required for suppression of nephrogenesis and progenitor renewal in the developing kidney. EMBO J 25:5214-5228
28. Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ (2004) A WNT4 mutation associated with Müllerian-duct regression and virilization in a 46, XX woman. N Engl J Med 351:792-798
29. Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, Indelman M, Drugan A, Tiosano D, Gershoni-Baruch R, Choder M, Sprecher E (2008) SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet 82:39-47
30. Vivante A, Mark-Danieli M, Davidovits M, Harari-Steinberg O, Omer D, Gnatek Y, Cleper R, Landau D, Kovalski Y, Weissman I, Eisenstein I, Soudack M, Wolf HR, Issler N, Lotan D, Anikster Y, Dekel B (2013) Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling. J Am Soc Nephrol 24:550-558
31. Brockschmidt A, Chung B, Weber S, Fischer DC, Kolatsi-Joannou M, Christ L, Heimbach A, Shtiza D, Klaus G, Simonetti GD, Konrad M, Winyard P, Haffner D, Schaefer F, Weber RG (2012) CHD1L: a new candidate gene for congenital anomalies of the kidneys and urinary tract (CAKUT). Nephrol Dial Transplant 27:2355-2364
32. Sanna-Cherchi S, Sampogna RV, Papeta N, Burgess KE, Nees SN, Perry BJ, Choi M, Bodria M, Liu Y, Weng PL, Lozanovski VJ, Verbitsky M, Lugani F, Sterken R, Paragas N, Caridi G, Carrea A, Dagnino M, Materna-Kiryluk A, Santamaria G, Murtas C, Ristoska-Bojkovska N, Izzi C, Kacak N, Bianco B, Giberti S, Gigante M, Piaggio G, Gesualdo L, Vukic DK, Vukojevic K, Saraga-Babic M, Saraga M, Gucev Z, Allegri L, Latos-Bielenska A, Casu D, State M, Scolari F, Ravazzolo R, Kiryluk K, Al-Awqati Q, D'Agati VD, Drummond IA, Tasic V, Lifton RP, Ghiggeri GM, Gharavi AG (2013) Mutations in DSTYK and dominant urinary tract malformations. N Engl J Med 369:621-629
33. 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 39:882-892
34. Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert M, Antignac C, Gubler MC (2005) Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet 37:964-968
35. Gribouval O, Moriniere V, Pawtowski A, Arrondel C, Sallinen SL, Saloranta C, Clericuzio C, Viot G, Tantau J, Blesson S, Cloarec S, Machet MC, Chitayat D, Thauvin C, Laurent N, Sampson JR, Bernstein JA, Clemenson A, Prieur F, Daniel L, Levy-Mozziconacci A, Lachlan K, Alessandri JL, Cartault F, Riviere JP, Picard N, Baumann C, Delezoide AL, Belar Ortega M, Chassaing N, Labrune P, Yu S, Firth H, Wellesley D, Bitzan M, Alfares A, Braverman N, Krogh L, Tolmie J, Gaspar H, Doray B, Majore S, Bonneau D, Triau S, Loirat C, David A, Bartholdi D, Peleg A, Brackman D, Stone R, DeBerardinis R, Corvol P, Michaud A, Antignac C, Gubler MC (2012) Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. Hum Mutat 33:316-326
36. Barak H, Huh SH, Chen S, Jeanpierre C, Martinovic J, Parisot M, Bole-Feysot C, Nitschke P, Salomon R, Antignac C, Ornitz DM, Kopan R (2012) FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man. Dev Cell 22:1191-1207
37. Woolf AS, Stuart HM, Newman WG (2013) Genetics of human congenital urinary bladder disease. Pediatr Nephrol. doi: 10.1007/s00467-013-2472-1
38. Dressler GR (2009) Advances in early kidney specification, development and patterning. Development 136:3863-3874
39. Reidy KJ, Rosenblum ND (2009) Cell and molecular biology of kidney development. Semin Nephrol 29:321-337
40. Faa G, Gerosa C, Fanni D, Monga G, Zaffanello M, Van Eyken P, Fanos V (2012) Morphogenesis and molecular mechanisms involved in human kidney development. J Cell Physiol 227:1257-1268
41. Vainio S, Lin Y (2002) Coordinating early kidney development: lessons from gene targeting. Nat Rev Genet 3:533-543
42. Ichikawa I, Kuwayama F, Pope JCT, Stephens FD, Miyazaki Y (2002) Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT. Kidney Int 61:889-898
43. 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 Ret. Nature 367:380-383
44. Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372:679-683
45. Nishimura H, Yerkes E, Hohenfellner K, Miyazaki Y, Ma J, Hunley TE, Yoshida H, Ichiki T, Threadgill D, Phillips JA III, Hogan BM, Fogo A, Brock JW III, 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 3:1-10
46. Mackie GG, Stephens FD (1975) Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol 114:274-280
47. Santoro M, Carlomagno F, Romano A, Bottaro DP, Dathan NA, Grieco M, Fusco A, Vecchio G, Matoskova B, Kraus MH (1995) Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 267:381-383
48. Romeo G, Ronchetto P, Luo Y, Barone V, Seri M, Ceccherini I, Pasini B, Bocciardi R, Lerone M, Kaariainen H, Martucciello G (1994) Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease. Nature 367:377-378
49. Jeanpierre C, Mace G, Parisot M, Moriniere V, Pawtowsky A, Benabou M, Martinovic J, Amiel J, Attie-Bitach T, Delezoide AL, Loget P, Blanchet P, Gaillard D, Gonzales M, Carpentier W, Nitschke P, Tores F, Heidet L, Antignac C, Salomon R (2011) RET and GDNF mutations are rare in fetuses with renal agenesis or other severe kidney development defects. J Med Genet 48:497-504
50. Pini Prato A, Musso M, Ceccherini I, Mattioli G, Giunta C, Ghiggeri GM, Jasonni V (2009) Hirschsprung disease and congenital anomalies of the kidney and urinary tract (CAKUT): a novel syndromic association. Medicine 88:83-90
51. Chatterjee R, Ramos E, Hoffman M, VanWinkle J, Martin DR, Davis TK, Hoshi M, Hmiel SP, Beck A, Hruska K, Coplen D, Liapis H, Mitra R, Druley T, Austin P, Jain S (2012) Traditional and targeted exome sequencing reveals common, rare and novel functional deleterious variants in RET-signaling complex in a cohort of living US patients with urinary tract malformations. Hum Genet 131:1725-1738
52. Weber S, Moriniere V, Knuppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiene A, Mir S, Montini G, Peco-Antic A, Wuhl 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 17:2864-2870
53. 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 24:2361-2368
54. Park JS, Ma W, O'Brien LL, Chung E, Guo JJ, Cheng JG, Valerius MT, McMahon JA, Wong WH, McMahon AP (2012) Six2 and Wnt regulate self-renewal and commitment of nephron progenitors through shared gene regulatory networks. Dev Cell 23:637-651
55. Okubo S, Niimura F, Matsusaka T, Fogo A, Hogan BL, Ichikawa I (1998) Angiotensinogen gene null-mutant mice lack homeostatic regulation of glomerular filtration and tubular reabsorption. Kidney Int 53:617-625
56. Tamm I, Horsfall FL Jr (1950) Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med 74:106-108
57. 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 24:55-60
58. Coffinier C, Thepot D, Babinet C, Yaniv M, Barra J (1999) Essential role for the homeoprotein vHNF1/HNF1beta in visceral endoderm differentiation. Development 126:4785-4794
59. Edghill EL, Bingham C, Ellard S, Hattersley AT (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84-90
60. Bellanne-Chantelot C, Chauveau D, Gautier JF, Dubois-Laforgue D, Clauin S, Beaufils S, Wilhelm JM, Boitard C, Noel LH, Velho G, Timsit J (2004) Clinical spectrum associated with hepatocyte nuclear factor-1beta mutations. Ann Intern Med 140:510-517
61. Adalat S, Woolf AS, Johnstone KA, Wirsing A, Harries LW, Long DA, Hennekam RC, Ledermann SE, Rees L, van't Hoff W, Marks SD, Trompeter RS, Tullus K, Winyard PJ, Cansick J, Mushtaq I, Dhillon HK, Bingham C, Edghill EL, Shroff R, Stanescu H, Ryffel GU, Ellard S, Bockenhauer D (2009) HNF1B mutations associate with hypomagnesemia and renal magnesium wasting. J Am Soc Nephrol 20:1123-1131
62. Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, Adam MP, Pakula AT, Eisenhauer NJ, Uhas K, Weik L, Guy L, Care ME, Morel CF, Boni C, Salbert BA, Chandrareddy A, Demmer LA, Chow EW, Surti U, Aradhya S, Pickering DL, Golden DM, Sanger WG, Aston E, Brothman AR, Gliem TJ, Thorland EC, Ackley T, Iyer R, Huang S, Barber JC, Crolla JA, Warren ST, Martin CL, Ledbetter DH (2010) Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet 87:618-630
63. Loirat C, Bellanne-Chantelot C, Husson I, Deschenes G, Guigonis V, Chabane N (2010) Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion. Nephrol Dial Transplant 25:3430-3433
64. Hiesberger T, Bai Y, Shao X, McNally BT, Sinclair AM, Tian X, Somlo S, Igarashi P (2004) Mutation of hepatocyte nuclear factor-1beta inhibits Pkhd1 gene expression and produces renal cysts in mice. J Clin Invest 113:814-825
65. Thomas R, Sanna-Cherchi S, Warady BA, Furth SL, Kaskel FJ, Gharavi AG (2011) HNF1B and PAX2 mutations are a common cause of renal hypodysplasia in the CKiD cohort. Pediatr Nephrol 26:897-903
66. Madariaga L, Moriniere V, Jeanpierre C, Bouvier R, Loget P, Martinovic J, Dechelotte P, Leporrier N, Thauvin-Robinet C, Jensen UB, Gaillard D, Mathieu M, Turlin B, Attie-Bitach T, Salomon R, Gubler MC, Antignac C, Heidet L (2013) Severe prenatal renal anomalies associated with mutations in HNF1B or PAX2 genes. Clin J Am Soc Nephrol 8:1179-1187
67. Weber S, Landwehr C, Renkert M, Hoischen A, Wuhl E, Denecke J, Radlwimmer B, Haffner D, Schaefer F, Weber RG (2011) Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Nephrol Dial Transplant 26:136-143
68. Sanna-Cherchi S, Kiryluk K, Burgess KE, Bodria M, Sampson MG, Hadley D, Nees SN, Verbitsky M, Perry BJ, Sterken R, Lozanovski VJ, Materna-Kiryluk A, Barlassina C, Kini A, Corbani V, Carrea A, Somenzi D, Murtas C, Ristoska-Bojkovska N, Izzi C, Bianco B, Zaniew M, Flogelova H, Weng PL, Kacak N, Giberti S, Gigante M, Arapovic A, Drnasin K, Caridi G, Curioni S, Allegri F, Ammenti A, Ferretti S, Goj V, Bernardo L, Jobanputra V, Chung WK, Lifton RP, Sanders S, State M, Clark LN, Saraga M, Padmanabhan S, Dominiczak AF, Foroud T, Gesualdo L, Gucev Z, Allegri L, Latos-Bielenska A, Cusi D, Scolari F, Tasic V, Hakonarson H, Ghiggeri GM, Gharavi AG (2012) Copy-number disorders are a common cause of congenital kidney malformations. Am J Hum Genet 91:987-997
69. Puri P, Gosemann JH, Darlow J, Barton DE (2011) Genetics of vesicoureteral reflux. Nat Rev Urol 8:539-552
70. Ruf RG, Berkman J, Wolf MT, Nurnberg P, Gattas M, Ruf EM, Hyland V, Kromberg J, Glass I, Macmillan J, Otto E, Nurnberg G, Lucke B, Hennies HC, Hildebrandt F (2003) A gene locus for branchio-otic syndrome maps to chromosome 14q21.3-q24.3. J Med Genet 40:515-519
71. Esther CR, Marino EM, Howard TE, Machaud A, Corvol P, Capecchi MR, Bernstein KE (1997) The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. J Clin Invest 99:2375-2385
72. Saisawat P, Kohl S, Hilger AC, Hwang DY, Yung Gee H, Dworschak GC, Tasic V, Pennimpede T, Natarajan S, Sperry E, Matassa DS, Stajić N, Bogdanovic R, de Blaauw I, Marcelis CL, Wijers CH, Bartels E, Schmiedeke E, Schmidt D, Märzheuser S, Grasshoff-Derr S, Holland-Cunz S, Ludwig M, Nöthen MM, Draaken M, Brosens E, Heij H, Tibboel D, Herrmann BG, Solomon BD, de Klein A, van Rooij IA, Esposito F, Reutter HM, Hildebrandt F (2013) Kidney Int. doi: 10.1038/ki.2013.417
73. McGregor L, Makela V, Darling SM, Vrontou S, Chalepakis G, Roberts C, Smart N, Rutland P, Prescott N, Hopkins J, Bentley E, Shaw A, Roberts E, Mueller R, Jadeja S, Philip N, Nelson J, Francannet C, Perez-Aytes A, Megarbane A, Kerr B, Wainwright B, Woolf AS, Winter RM, Scambler PJ (2003) Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein. Nat Genet 34:203-208
74. Jadeja S, Smyth I, Pitera JE, Taylor MS, van Haelst M, Bentley E, McGregor L, Hopkins J, Chalepakis G, Philip N, Perez Aytes A, Watt FM, Darling SM, Jackson I, Woolf AS, Scambler PJ (2005) Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs. Nat Genet 37:520-525
75. Kirby A, Gnirke A, Jaffe DB, Barešová V, Pochet N, Blumenstiel B, Ye C, Aird D, Stevens C, Robinson JT, Cabili MN, Gat-Viks I, Kelliher E, Daza R, DeFelice M,Hůlková H, Sovová J, Vylet'al P, Antignac C, Guttman M, Handsaker RE, Perrin D, Steelman S, Sigurdsson S, Scheinman SJ, Sougnez C, Cibulskis K, Parkin M,Green T, Rossin E, Zody MC, Xavier RJ, Pollak MR, Alper SL, Lindblad-Toh K, Gabriel S, Hart PS, Regev A, Nusbaum C, Kmoch S, Bleyer AJ, Lander ES, Daly MJ (2013) Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet 45(3):299-303