Abstract
Renal hypoplasia, defined as abnormally small kidneys with normal morphology and reduced nephron number, is a common cause of pediatric renal failure and adult-onset disease. Genetic studies performed in humans and mutant mice have implicated a number of critical genes, in utero environmental factors and molecular mechanisms that regulate nephron endowment and kidney size. Here, we review current knowledge regarding the genetic contributions to renal hypoplasia with particular emphasis on the mechanisms that control nephron endowment in humans and mice.
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Abbreviations
- FGF(R):
-
fibroblast growth factor (receptor)
- HH:
-
Hedgehog
- MM:
-
metanephric mesenchyme
- Rar:
-
retinoic acid receptor
- UB:
-
ureteric bud
- UBM:
-
ureteric branching morphogenesis
References
Hiraoka M, Tsukahara H, Ohshima Y, Kasuga K, Ishihara Y, Mayumi M 2002 Renal aplasia is the predominant cause of congenital solitary kidneys. Kidney Int 61: 1840–1844
Brenner BM, Chertow GM 1994 Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis 23: 171–175
Brenner BM, Garcia DL, Anderson S 1988 Glomeruli and blood pressure. Less of one, more the other?. Am J Hypertens 1: 335–347
Hoy WE, Hughson MD, Singh GR, Douglas-Denton R, Bertram JF 2006 Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int 70: 104–110
Hughson MD, Douglas-Denton R, Bertram JF, Hoy WE 2006 Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int 69: 671–678
Keller G, Zimmer G, Mall G, Ritz E, Amann K 2003 Nephron number in patients with primary hypertension. N Engl J Med 348: 101–108
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
Schedl A 2007 Renal abnormalities and their developmental origin. Nat Rev Genet 8: 791–802
Woolf AS, Price KL, Scambler PJ, Winyard PJ 2004 Evolving concepts in human renal dysplasia. J Am Soc Nephrol 15: 998–1007
Hoy WE, Douglas-Denton RN, Hughson MD, Cass A, Johnson K, Bertram JF 2003 A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl 63: S31–S37
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
Jijiwa M, Fukuda T, Kawai K, Nakamura A, Kurokawa K, Murakumo Y, Ichihara M, Takahashi M 2004 A targeting mutation of tyrosine 1062 in Ret causes a marked decrease of enteric neurons and renal hypoplasia. Mol Cell Biol 24: 8026–8036
Schmidt W, Schroeder TM, Buchinger G, Kubli F 1982 Genetics, pathoanatomy and prenatal diagnosis of Potter I syndrome and other urogenital tract diseases. Clin Genet 22: 105–127
Zhang Z, Quinlan J, Hoy W, Hughson MD, Lemire M, Hudson T, Hueber PA, Benjamin A, Roy A, Pascuet E, Goodyer M, Raju C, Houghton F, Bertram J, Goodyer P 2008 A common RET variant is associated with reduced newborn kidney size and function. J Am Soc Nephrol 19: 2027–2034
Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP 2003 Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development 130: 3175–3185
Sims-Lucas S, Cullen-McEwen L, Eswarakumar VP, Hains D, Kish K, Becknell B, Zhang J, Bertram JF, Wang F, Bates CM 2009 Deletion of Frs2alpha from the ureteric epithelium causes renal hypoplasia. Am J Physiol Renal Physiol 297: F1208–F1219
Zhao H, Kegg H, Grady S, Truong HT, Robinson ML, Baum M, Bates CM 2004 Role of fibroblast growth factor receptors 1 and 2 in the ureteric bud. Dev Biol 276: 403–415
Lu BC, Cebrian C, Chi X, Kuure S, Kuo R, Bates CM, Arber S, Hassell J, MacNeil L, Hoshi M, Jain S, Asai N, Takahashi M, Schmidt-Ott KM, Barasch J, D'Agati V, Costantini F 2009 Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet 41: 1295–1302
Ishibe S, Karihaloo A, Ma H, Zhang J, Marlier A, Mitobe M, Togawa A, Schmitt R, Czyczk J, Kashgarian M, Geller DS, Thorgeirsson SS, Cantley LG 2009 Met and the epidermal growth factor receptor act cooperatively to regulate final nephron number and maintain collecting duct morphology. Development 136: 337–345
Zhang Z, Pascuet E, Hueber PA, Chu L, Bichet DG, Lee TC, Threadgill DW, Goodyer P 2010 Targeted Inactivation of EGF Receptor Inhibits Renal Collecting Duct Development and Function. J Am Soc Nephrol 21: 573–578
Kobayashi A, Kwan KM, Carroll TJ, McMahon AP, Mendelsohn CL, Behringer RR 2005 Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development 132: 2809–2823
Chung GW, Edwards AO, Schimmenti LA, Manligas GS, Zhang YH, Ritter R III 2001 Renal-coloboma syndrome: report of a novel PAX2 gene mutation. Am J Ophthalmol 132: 910–914
Ford B, Rupps R, Lirenman D, Van Allen MI, Farquharson D, Lyons C, Friedman JM 2001 Renal-coloboma syndrome: prenatal detection and clinical spectrum in a large family. Am J Med Genet 99: 137–141
Parsa CF, Silva ED, Sundin OH, Goldberg MF, De Jong MR, Sunness JS, Zeimer R, Hunter DG 2001 Redefining papillorenal syndrome: an underdiagnosed cause of ocular and renal morbidity. Ophthalmology 108: 738–749
Nishimoto K, Iijima K, Shirakawa T, Kitagawa K, Satomura K, Nakamura H, Yoshikawa N 2001 PAX2 gene mutation in a family with isolated renal hypoplasia. J Am Soc Nephrol 12: 1769–1772
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: 1915–1921
Porteous S, Torban E, Cho NP, Cunliffe H, Chua L, McNoe L, Ward T, Souza C, Gus P, Giugliani R, Sato T, Yun K, Favor J, Sicotte M, Goodyer P, Eccles M 2000 Primary renal hypoplasia in humans and mice with PAX2 mutations: evidence of increased apoptosis in fetal kidneys of Pax2(1Neu) +/− mutant mice. Hum Mol Genet 9: 1–11
Dziarmaga A, Eccles M, Goodyer P 2006 Suppression of ureteric bud apoptosis rescues nephron endowment and adult renal function in Pax2 mutant mice. J Am Soc Nephrol 17: 1568–1575
Dziarmaga A, Clark P, Stayner C, Julien JP, Torban E, Goodyer P, Eccles M 2003 Ureteric bud apoptosis and renal hypoplasia in transgenic PAX2-Bax fetal mice mimics the renal-coloboma syndrome. J Am Soc Nephrol 14: 2767–2774
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: 3420–3428
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: 347–357
Bingham C, Ellard S, van't Hoff WG, Simmonds HA, Marinaki AM, Badman MK, Winocour PH, Stride A, Lockwood CR, Nicholls AJ, Owen KR, Spyer G, Pearson ER, Hattersley AT 2003 Atypical familial juvenile hyperuricemic nephropathy associated with a hepatocyte nuclear factor-1beta gene mutation. Kidney Int 63: 1645–1651
Godley LA, Kopp JB, Eckhaus M, Paglino JJ, Owens J, Varmus HE 1996 Wild-type p53 transgenic mice exhibit altered differentiation of the ureteric bud and possess small kidneys. Genes Dev 10: 836–850
Cain JE, Islam E, Haxho F, Chen L, Bridgewater D, Nieuwenhuis E, Hui CC, Rosenblum ND 2009 GLI3 repressor controls nephron number via regulation of Wnt11 and Ret in ureteric tip cells. PLoS One 4: e7313
Sama A, Mason JD, Gibbin KP, Young ID, Hewitt M 1994 The Pallister-Hall syndrome. J Med Genet 31: 740
Johnston JJ, Olivos-Glander I, Killoran C, Elson E, Turner JT, Peters KF, Abbott MH, Aughton DJ, Aylsworth AS, Bamshad MJ, Booth C, Curry CJ, David A, Dinulos MB, Flannery DB, Fox MA, Graham JM, Grange DK, Guttmacher AE, Hannibal MC, Henn W, Hennekam RC, Holmes LB, Hoyme HE, Leppig KA, Lin AE, Macleod P, Manchester DK, Marcelis C, Mazzanti L, McCann E, McDonald MT, Mendelsohn NJ, Moeschler JB, Moghaddam B, Neri G, Newbury-Ecob R, Pagon RA, Phillips JA, Sadler LS, Stoler JM, Tilstra D, Walsh Vockley CM, Zackai EH, Zadeh TM, Brueton L, Black GC, Biesecker LG 2005 Molecular and clinical analyses of Greig cephalopolysyndactyly and Pallister-Hall syndromes: robust phenotype prediction from the type and position of GLI3 mutations. Am J Hum Genet 76: 609–622
Donnai D, Young ID, Owen WG, Clark SA, Miller PF, Knox WF 1986 The lethal multiple congenital anomaly syndrome of polydactyly, sex reversal, renal hypoplasia, and unilobular lungs. J Med Genet 23: 64–71
Moore MW, Klein RD, Farinas I, Sauer H, Armanini M, Phillips H, Reichardt LF, Ryan AM, Carver-Moore K, Rosenthal A 1996 Renal and neuronal abnormalities in mice lacking GDNF. Nature 382: 76–79
Pichel JG, Shen L, Sheng HZ, Granholm AC, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H 1996 Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382: 73–76
Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M 1996 Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382: 70–73
Cullen-McEwen LA, Drago J, Bertram JF 2001 Nephron endowment in glial cell line-derived neurotrophic factor (GDNF) heterozygous mice. Kidney Int 60: 31–36
Cullen-McEwen LA, Kett MM, Dowling J, Anderson WP, Bertram JF 2003 Nephron number, renal function, and arterial pressure in aged GDNF heterozygous mice. Hypertension 41: 335–340
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: 1151–1157
Davis AP, Witte DP, Hsieh-Li HM, Potter SS, Capecchi MR 1995 Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. Nature 375: 791–795
Esquela AF, Lee SJ 2003 Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 257: 356–370
Patterson LT, Pembaur M, Potter SS 2001 Hoxa11 and Hoxd11 regulate branching morphogenesis of the ureteric bud in the developing kidney. Development 128: 2153–2161
Xu PX, Adams J, Peters H, Brown MC, Heaney S, Maas R 1999 Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia. Nat Genet 23: 113–117
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
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
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
Nishinakamura R, Matsumoto Y, Nakao K, Nakamura K, Sato A, Copeland NG, Gilbert DJ, Jenkins NA, Scully S, Lacey DL, Katsuki M, Asashima M, Yokota T 2001 Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development. Development 128: 3105–3115
Warren M, Wang W, Spiden S, Chen-Murchie D, Tannahill D, Steel KP, Bradley A 2007 A Sall4 mutant mouse model useful for studying the role of Sall4 in early embryonic development and organogenesis. Genesis 45: 51–58
Becker K, Beales PL, Calver DM, Matthijs G, Mohammed SN 2002 Okihiro syndrome and acro-renal-ocular syndrome: clinical overlap, expansion of the phenotype, and absence of PAX2 mutations in two new families. J Med Genet 39: 68–71
Newman WG, Brunet MD, Donnai D 1997 Townes-Brocks syndrome presenting as end stage renal failure. Clin Dysmorphol 6: 57–60
Mendelsohn C, Lohnes D, Decimo D, Lufkin T, LeMeur M, Chambon P, Mark M 1994 Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development 120: 2749–2771
Rosselot C, Spraggon L, Chia I, Batourina E, Riccio P, Lu B, Niederreither K, Dolle P, Duester G, Chambon P, Costantini F, Gilbert T, Molotkov A, Mendelsohn C 2010 Non-cell-autonomous retinoid signaling is crucial for renal development. Development 137: 283–292
Batourina E, Gim S, Bello N, Shy M, Clagett-Dame M, Srinivas S, Costantini F, Mendelsohn C 2001 Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Nat Genet 27: 74–78
Lelievre-Pegorier M, Vilar J, Ferrier ML, Moreau E, Freund N, Gilbert T, Merlet-Benichou C 1998 Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int 54: 1455–1462
Wilson JG, Roth CB, Warkany J 1953 An analysis of the syndrome of malformations induced by maternal vitamin A deficiency. Effects of restoration of vitamin A at various times during gestation. Am J Anat 92: 189–217
Qiao J, Uzzo R, Obara-Ishihara T, Degenstein L, Fuchs E, Herzlinger D 1999 FGF-7 modulates ureteric bud growth and nephron number in the developing kidney. Development 126: 547–554
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: e1000809
Ohuchi H, Hori Y, Yamasaki M, Harada H, Sekine K, Kato S, Itoh N 2000 FGF10 acts as a major ligand for FGF receptor 2 IIIb in mouse multi-organ development. Biochem Biophys Res Commun 277: 643–649
Bates CM, Kharzai S, Erwin T, Rossant J, Parada LF 2000 Role of N-myc in the developing mouse kidney. Dev Biol 222: 317–325
Couillard M, Trudel M 2009 C-myc as a modulator of renal stem/progenitor cell population. Dev Dyn 238: 405–414
Novack DV, Korsmeyer SJ 1994 Bcl-2 protein expression during murine development. Am J Pathol 145: 61–73
Nagata M, Nakauchi H, Nakayama K, Nakayama K, Loh D, Watanabe T 1996 Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bcl-2-deficient mice. Am J Pathol 148: 1601–1611
Sorenson CM, Rogers SA, Korsmeyer SJ, Hammerman MR 1995 Fulminant metanephric apoptosis and abnormal kidney development in bcl-2-deficient mice. Am J Physiol 268: F73–F81
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: 169–181
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
Fogelgren B, Yang S, Sharp IC, Huckstep OJ, Ma W, Somponpun SJ, Carlson EC, Uyehara CF, Lozanoff S 2009 Deficiency in Six2 during prenatal development is associated with reduced nephron number, chronic renal failure, and hypertension in Br/+ adult mice. Am J Physiol Renal Physiol 296: F1166–F1178
Denton KM 2006 Can adult cardiovascular disease be programmed in utero?. J Hypertens 24: 1245–1247
Moritz KM, Dodic M, Wintour EM 2003 Kidney development and the fetal programming of adult disease. Bioessays 25: 212–220
Wlodek ME, Mibus A, Tan A, Siebel AL, Owens JA, Moritz KM 2007 Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol 18: 1688–1696
Zohdi V, Moritz KM, Bubb KJ, Cock ML, Wreford N, Harding R, Black MJ 2007 Nephrogenesis and the renal renin-angiotensin system in fetal sheep: effects of intrauterine growth restriction during late gestation. Am J Physiol Regul Integr Comp Physiol 293: R1267–R1273
Brennan KA, Kaufman S, Reynolds SW, McCook BT, Kan G, Christiaens I, Symonds ME, Olson DM 2008 Differential effects of maternal nutrient restriction through pregnancy on kidney development and later blood pressure control in the resulting offspring. Am J Physiol Regul Integr Comp Physiol 295: R197–R205
Gilbert JS, Lang AL, Grant AR, Nijland MJ 2005 Maternal nutrient restriction in sheep: hypertension and decreased nephron number in offspring at 9 months of age. J Physiol 565: 137–147
Hoppe CC, Evans RG, Bertram JF, Moritz KM 2007 Effects of dietary protein restriction on nephron number in the mouse. Am J Physiol Regul Integr Comp Physiol 292: R1768–R1774
Makrakis J, Zimanyi MA, Black MJ 2007 Retinoic acid enhances nephron endowment in rats exposed to maternal protein restriction. Pediatr Nephrol 22: 1861–1867
Pires KM, Aguila MB, Mandarim-de-Lacerda CA 2006 Early renal structure alteration in rat offspring from dams fed low protein diet. Life Sci 79: 2128–2134
Villar-Martini VC, Carvalho JJ, Neves MF, Aguila MB, Mandarim-de-Lacerda CA 2009 Hypertension and kidney alterations in rat offspring from low protein pregnancies. J Hypertens 27: S47–S51
Abdel-Hakeem AK, Henry TQ, Magee TR, Desai M, Ross MG, Mansano RZ, Torday JS, Nast CC 2008 Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression. Am J Obstet Gynecol 199: 252.e1–252.e7
Welham SJ, Riley PR, Wade A, Hubank M, Woolf AS 2005 Maternal diet programs embryonic kidney gene expression. Physiol Genomics 22: 48–56
Amri K, Freund N, Vilar J, Merlet-Benichou C, Lelievre-Pegorier M 1999 Adverse effects of hyperglycemia on kidney development in rats: in vivo and in vitro studies. Diabetes 48: 2240–2245
Battin M, Albersheim S, Newman D 1995 Congenital genitourinary tract abnormalities following cocaine exposure in utero. Am J Perinatol 12: 425–428
Chasnoff IJ, Chisum GM, Kaplan WE 1988 Maternal cocaine use and genitourinary tract malformations. Teratology 37: 201–204
Rosenstein BJ, Wheeler JS, Heid PL 1990 Congenital renal abnormalities in infants with in utero cocaine exposure. J Urol 144: 110–112
Havers W, Majewski F, Olbing H, Eickenberg HU 1980 Anomalies of the kidneys and genitourinary tract in alcoholic embryopathy. J Urol 124: 108–110
Qazi Q, Masakawa A, Milman D, McGann B, Chua A, Haller J 1979 Renal anomalies in fetal alcohol syndrome. Pediatrics 63: 886–889
Taylor CL, Jones KL, Jones MC, Kaplan GW 1994 Incidence of renal anomalies in children prenatally exposed to ethanol. Pediatrics 94: 209–212
Gray SP, Kenna K, Bertram JF, Hoy WE, Yan EB, Bocking AD, Brien JF, Walker DW, Harding R, Moritz KM 2008 Repeated ethanol exposure during late gestation decreases nephron endowment in fetal sheep. Am J Physiol Regul Integr Comp Physiol 295: R568–R574
Dickinson H, Walker DW, Wintour EM, Moritz K 2007 Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse. Am J Physiol Regul Integr Comp Physiol 292: R453–R461
Dodic M, Abouantoun T, O'Connor A, Wintour EM, Moritz KM 2002 Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension 40: 729–734
Singh RR, Cullen-McEwen LA, Kett MM, Boon WM, Dowling J, Bertram JF, Moritz KM 2007 Prenatal corticosterone exposure results in altered AT1/AT2, nephron deficit and hypertension in the rat offspring. J Physiol 579: 503–513
Singh RR, Moritz KM, Bertram JF, Cullen-McEwen LA 2007 Effects of dexamethasone exposure on rat metanephric development: in vitro and in vivo studies. Am J Physiol Renal Physiol 293: F548–F554
Wintour EM, Moritz KM, Johnson K, Ricardo S, Samuel CS, Dodic M 2003 Reduced nephron number in adult sheep, hypertensive as a result of prenatal glucocorticoid treatment. J Physiol 549: 929–935
McBride WG 1977 Thalidomide embryopathy. Teratology 16: 79–82
Smithells RW, Newman CG 1992 Recognition of thalidomide defects. J Med Genet 29: 716–723
Kanjilal D, Basir MA, Verma RS, Rajegowda BK, Lala R, Nagaraj A 1992 New dysmorphic features in Rubinstein-Taybi syndrome. J Med Genet 29: 669–670
Chitayat D, Hodgkinson KA, Chen MF, Haber GD, Nakishima S, Sando I 1992 Branchio-oto-renal syndrome: further delineation of an underdiagnosed syndrome. Am J Med Genet 43: 970–975
Slavotinek AM, Tifft CJ 2002 Fraser syndrome and cryptophthalmos: review of the diagnostic criteria and evidence for phenotypic modules in complex malformation syndromes. J Med Genet 39: 623–633
Ounap K, Laidre P, Bartsch O, Rein R, Lipping-Sitska M 1998 Familial Williams-Beuren syndrome. Am J Med Genet 80: 491–493
Grix A Jr, Curry C, Hall BD 1982 Patterns of multiple malformations in infants of diabetic mothers. Birth Defects Orig Artic Ser 18: 55–77
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Supported by grants awarded by the Canadian Institute of Health research and The Canada Research Chair Program (N.D.R.).
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Cain, J., Di Giovanni, V., Smeeton, J. et al. Genetics of Renal Hypoplasia: Insights Into the Mechanisms Controlling Nephron Endowment. Pediatr Res 68, 91–98 (2010). https://doi.org/10.1203/PDR.0b013e3181e35a88
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DOI: https://doi.org/10.1203/PDR.0b013e3181e35a88
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