Advertisement

Pediatric Nephrology

, Volume 29, Issue 4, pp 695–704 | Cite as

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

  • Asaf Vivante
  • Stefan Kohl
  • Daw-Yang Hwang
  • Gabriel C. Dworschak
  • Friedhelm HildebrandtEmail author
Review

Abstract

Congenital anomalies of the kidney and urinary tract (CAKUT) cover a wide range of structural malformations that result from defects in the morphogenesis of the kidney and/or urinary tract. These anomalies account for about 40–50 % of children with chronic kidney disease worldwide. Knowledge from genetically modified mouse models suggests that single gene mutations in renal developmental genes may lead to CAKUT in humans. However, until recently, only a handful of CAKUT-causing genes were reported, most of them in familial syndromic cases. Recent findings suggest that CAKUT may arise from mutations in a multitude of different single gene causes. We focus here on single-gene causes of CAKUT and their developmental origin. Currently, more than 20 monogenic CAKUT-causing genes have been identified. High-throughput sequencing techniques make it likely that additional CAKUT-causing genes will be identified in the near future.

Keywords

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

Notes

Acknowledgments

F.H. is an Investigator of the Howard Hughes Medical Institute, a Doris Duke Distinguished Clinical Scientist, and the Warren E. Grupe Professor of Pediatrics. This research was supported by grants from the National Institutes of Health (to F.H.; R01-DK088767) and by the March of Dimes Foundation (6FY11-241). A.V. is a recipient of the Fulbright Post-doctoral Scholar Award for 2013. A.V. is also supported by grants from the Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel-Hashomer, Israel and the Manton center Fellowship program, Boston Children’s Hospital, Boston, MA.

References

  1. 1.
    Schedl A (2007) Renal abnormalities and their developmental origin. Nat Rev Genet 8:791–802PubMedCrossRefGoogle Scholar
  2. 2.
    (2008) North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (2008) 2008 Annual report. The EMMES Corporation, Rockville, MDGoogle Scholar
  3. 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 9:358–364PubMedCrossRefGoogle Scholar
  4. 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 8:2001–2008PubMedCrossRefGoogle Scholar
  5. 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 15:157–164PubMedCrossRefGoogle Scholar
  6. 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 28:2143–2147PubMedCrossRefGoogle Scholar
  7. 7.
    Yosypiv IV (2012) Congenital anomalies of the kidney and urinary tract: a genetic disorder? Int J Nephrol. doi: 10.1155/2012/909083 Google Scholar
  8. 8.
    Chen F (2009) Genetic and developmental basis for urinary tract obstruction. Pediatr Nephrol 24:1621–1632PubMedCentralPubMedCrossRefGoogle Scholar
  9. 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 26:3843–3851PubMedCrossRefGoogle Scholar
  10. 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 22:1675–1684PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Weber S (2012) Novel genetic aspects of congenital anomalies of kidney and urinary tract. Curr Opin Pediatr 24:212–218PubMedCrossRefGoogle Scholar
  12. 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 19:891–903PubMedCrossRefGoogle Scholar
  13. 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 11:40–44PubMedCrossRefGoogle Scholar
  14. 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 406:419–422PubMedCrossRefGoogle Scholar
  15. 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 17:384–385PubMedCrossRefGoogle Scholar
  16. 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 89:8190–8194PubMedCrossRefGoogle Scholar
  17. 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 33:457–466PubMedCrossRefGoogle Scholar
  18. 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 82:344–351PubMedCentralPubMedCrossRefGoogle Scholar
  19. 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 29:695–702PubMedCrossRefGoogle Scholar
  20. 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 80:616–632PubMedCentralPubMedCrossRefGoogle Scholar
  21. 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 18:81–83PubMedCrossRefGoogle Scholar
  22. 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 101:8090–8095PubMedCrossRefGoogle Scholar
  23. 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 80:800–804PubMedCentralPubMedCrossRefGoogle Scholar
  24. 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 31:1352–1359PubMedCentralPubMedCrossRefGoogle Scholar
  25. 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 24:1313–1322PubMedCrossRefGoogle Scholar
  26. 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 16:2141–2149PubMedCrossRefGoogle Scholar
  27. 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 25:5214–5228PubMedCrossRefGoogle Scholar
  28. 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 351:792–798PubMedCrossRefGoogle Scholar
  29. 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 82:39–47PubMedCentralPubMedCrossRefGoogle Scholar
  30. 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 24:550–558PubMedCrossRefGoogle Scholar
  31. 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 27:2355–2364PubMedCrossRefGoogle Scholar
  32. 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 369:621–629PubMedCrossRefGoogle Scholar
  33. 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 39:882–892PubMedCrossRefGoogle Scholar
  34. 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 37:964–968PubMedCrossRefGoogle Scholar
  35. 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 33:316–326PubMedCrossRefGoogle Scholar
  36. 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 22:1191–1207PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Woolf AS, Stuart HM, Newman WG (2013) Genetics of human congenital urinary bladder disease. Pediatr Nephrol. doi: 10.1007/s00467-013-2472-1 Google Scholar
  38. 38.
    Dressler GR (2009) Advances in early kidney specification, development and patterning. Development 136:3863–3874PubMedCrossRefGoogle Scholar
  39. 39.
    Reidy KJ, Rosenblum ND (2009) Cell and molecular biology of kidney development. Semin Nephrol 29:321–337PubMedCentralPubMedCrossRefGoogle Scholar
  40. 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 227:1257–1268PubMedCrossRefGoogle Scholar
  41. 41.
    Vainio S, Lin Y (2002) Coordinating early kidney development: lessons from gene targeting. Nat Rev Genet 3:533–543PubMedCrossRefGoogle Scholar
  42. 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 61:889–898PubMedCrossRefGoogle Scholar
  43. 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 367:380–383PubMedCrossRefGoogle Scholar
  44. 44.
    Stark K, Vainio S, Vassileva G, McMahon AP (1994) Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature 372:679–683PubMedCrossRefGoogle Scholar
  45. 45.
    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 3:1–10PubMedCrossRefGoogle Scholar
  46. 46.
    Mackie GG, Stephens FD (1975) Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol 114:274–280PubMedGoogle Scholar
  47. 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 267:381–383PubMedCrossRefGoogle Scholar
  48. 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 367:377–378PubMedCrossRefGoogle Scholar
  49. 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 48:497–504PubMedCrossRefGoogle Scholar
  50. 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 88:83–90PubMedCrossRefGoogle Scholar
  51. 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 131:1725–1738PubMedCentralPubMedCrossRefGoogle Scholar
  52. 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 17:2864–2870PubMedCrossRefGoogle Scholar
  53. 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 24:2361–2368PubMedCrossRefGoogle Scholar
  54. 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 23:637–651PubMedCentralPubMedCrossRefGoogle Scholar
  55. 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 53:617–625PubMedCrossRefGoogle Scholar
  56. 56.
    Tamm I, Horsfall FL Jr (1950) Characterization and separation of an inhibitor of viral hemagglutination present in urine. Proc Soc Exp Biol Med 74:106–108PubMedCrossRefGoogle Scholar
  57. 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 24:55–60PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Coffinier C, Thepot D, Babinet C, Yaniv M, Barra J (1999) Essential role for the homeoprotein vHNF1/HNF1beta in visceral endoderm differentiation. Development 126:4785–4794PubMedGoogle Scholar
  59. 59.
    Edghill EL, Bingham C, Ellard S, Hattersley AT (2006) Mutations in hepatocyte nuclear factor-1beta and their related phenotypes. J Med Genet 43:84–90PubMedCrossRefGoogle Scholar
  60. 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 140:510–517PubMedCrossRefGoogle Scholar
  61. 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 20:1123–1131PubMedCrossRefGoogle Scholar
  62. 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 87:618–630PubMedCentralPubMedCrossRefGoogle Scholar
  63. 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 25:3430–3433PubMedCrossRefGoogle Scholar
  64. 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 113:814–825PubMedCentralPubMedCrossRefGoogle Scholar
  65. 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 26:897–903PubMedCentralPubMedCrossRefGoogle Scholar
  66. 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 8:1179–1187PubMedCrossRefGoogle Scholar
  67. 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 26:136–143PubMedCrossRefGoogle Scholar
  68. 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 91:987–997PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Puri P, Gosemann JH, Darlow J, Barton DE (2011) Genetics of vesicoureteral reflux. Nat Rev Urol 8:539–552PubMedCrossRefGoogle Scholar
  70. 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 40:515–519PubMedCrossRefGoogle Scholar
  71. 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 99:2375–2385PubMedCentralPubMedCrossRefGoogle Scholar
  72. 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 Google Scholar
  73. 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 34:203–208PubMedCrossRefGoogle Scholar
  74. 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 37:520–525PubMedCrossRefGoogle Scholar
  75. 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):299–303Google Scholar

Copyright information

© IPNA 2014

Authors and Affiliations

  • Asaf Vivante
    • 1
    • 2
  • Stefan Kohl
    • 1
  • Daw-Yang Hwang
    • 1
  • Gabriel C. Dworschak
    • 1
  • Friedhelm Hildebrandt
    • 1
    • 3
    Email author
  1. 1.Department of MedicineBoston Children’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Talpiot Medical Leadership ProgramSheba Medical CenterTel-HashomerIsrael
  3. 3.Howard Hughes Medical InstituteChevy ChaseUSA

Personalised recommendations