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The Renal Sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development

Abstract

The renal manifestations of Alagille syndrome (ALGS) are an under-recognized, but clinically important component of the syndrome. Abnormalities in the Notch signaling pathway as a consequence of JAG1 and NOTCH2 mutations result in the diverse manifestations of ALGS. Notch signaling plays a central role in the development of multiple tissues and organs but particularly of the kidneys. Understanding the role of Notch signaling in renal development helps inform clinicians as to the more common renal findings in ALGS and the expectation of renal disease in these patients. Additionally, the Notch signal pathway plays a role in the evolution of chronic renal injury. How that response to renal injury is altered in ALGS and its impact on the clinical sequelae in ALGS is not known. Given the frequency of renal findings in ALGS, kidney specialists should form part of the multidisciplinary care team for these patients.

Keywords

  • Alagille syndrome
  • Kidney
  • Renal
  • JAG1
  • Notch
  • Development
  • Manifestations
  • Sequelae

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References

  1. Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommergues JP. Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr. 1987;110(2):195–200.

    CAS  PubMed  CrossRef  Google Scholar 

  2. Spinner NB, Leonard LD, Krantz ID. Alagille syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, et al., editors. GeneReviews(R). Seattle (WA): University of Washington, Seattle University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved; 1993.

    Google Scholar 

  3. Turnpenny PD, Ellard S. Alagille syndrome: pathogenesis, diagnosis and management. Eur J Human Genet. 2012;20(3):251–7.

    CAS  CrossRef  Google Scholar 

  4. Li L, Krantz ID, Deng Y, Genin A, Banta AB, Collins CC, et al. Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1. Nat Genet. 1997;16(3):243–51.

    CAS  PubMed  CrossRef  Google Scholar 

  5. McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, et al. NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the NOTCH signaling pathway. Am J Hum Genet. 2006;79(1):169–73.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  6. Oda T, Elkahloun AG, Pike BL, Okajima K, Krantz ID, Genin A, et al. Mutations in the human Jagged1 gene are responsible for Alagille syndrome. Nat Genet. 1997;16(3):235–42.

    CAS  PubMed  CrossRef  Google Scholar 

  7. Kamath BM, Podkameni G, Hutchinson AL, Leonard LD, Gerfen J, Krantz ID, et al. Renal anomalies in Alagille syndrome: a disease-defining feature. Am J Med Genet A. 2012;158a(1):85–9.

    PubMed  CrossRef  CAS  Google Scholar 

  8. Kamath BM, Spinner NB, Rosenblum ND. Renal involvement and the role of Notch signalling in Alagille syndrome. Nat Rev Nephrol. 2013;9(7):409–18.

    CAS  PubMed  CrossRef  Google Scholar 

  9. Warthen DM, Moore EC, Kamath BM, Morrissette JJ, Sanchez-Lara PA, Piccoli DA, et al. Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate. Hum Mutat. 2006;27(5):436–43.

    CAS  PubMed  CrossRef  Google Scholar 

  10. Bauer RC, Laney AO, Smith R, Gerfen J, Morrissette JJ, Woyciechowski S, et al. Jagged1 (JAG1) mutations in patients with tetralogy of Fallot or pulmonic stenosis. Hum Mutat. 2010;31(5):594–601.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  11. Harendza S, Hubner CA, Glaser C, Burdelski M, Thaiss F, Hansmann I, et al. Renal failure and hypertension in Alagille syndrome with a novel JAG1 mutation. J Nephrol. 2005;18(3):312–7.

    CAS  PubMed  Google Scholar 

  12. Kamath BM, Bason L, Piccoli DA, Krantz ID, Spinner NB. Consequences of JAG1 mutations. J Med Genet. 2003;40(12):891–5.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  13. Krantz ID. Alagille syndrome: chipping away at the tip of the iceberg. Am J Med Genet. 2002;112(2):160–2.

    PubMed  CrossRef  Google Scholar 

  14. Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA. Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology. 1999;29(3):822–9.

    CAS  PubMed  CrossRef  Google Scholar 

  15. Subramaniam P, Knisely A, Portmann B, Qureshi SA, Aclimandos WA, Karani JB, et al. Diagnosis of Alagille syndrome-25 years of experience at King's College Hospital. J Pediatr Gastroenterol Nutr. 2011;52(1):84–9.

    CAS  PubMed  CrossRef  Google Scholar 

  16. Quiros-Tejeira RE, Ament ME, Heyman MB, Martin MG, Rosenthal P, Hall TR, et al. Variable morbidity in alagille syndrome: a review of 43 cases. J Pediatr Gastroenterol Nutr. 1999;29(4):431–7.

    CAS  PubMed  CrossRef  Google Scholar 

  17. Hoffenberg EJ, Narkewicz MR, Sondheimer JM, Smith DJ, Silverman A, Sokol RJ. Outcome of syndromic paucity of interlobular bile ducts (Alagille syndrome) with onset of cholestasis in infancy. J Pediatr. 1995;127(2):220–4.

    CAS  PubMed  CrossRef  Google Scholar 

  18. Bray SJ. Notch signalling in context. Nat Rev Mol Cell Biol. 2016;17(11):722–35.

    CAS  PubMed  CrossRef  Google Scholar 

  19. Masek J, Andersson ER. The developmental biology of genetic Notch disorders. Development. 2017;144(10):1743–63.

    CAS  PubMed  CrossRef  Google Scholar 

  20. Gridley T. Notch signaling and inherited disease syndromes. Human Mol Genet. 2003;12 Spec No 1:R9–13.

    CrossRef  CAS  Google Scholar 

  21. Kopan R, Chen S, Liu Z. Alagille, Notch, and robustness: why duplicating systems does not ensure redundancy. Pediatr Nephrol. 2014;29(4):651–7.

    PubMed  CrossRef  Google Scholar 

  22. Kopan R, Ilagan MX. The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009;137(2):216–33.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  23. Sirin Y, Susztak K. Notch in the kidney: development and disease. J Pathol. 2012;226(2):394–403.

    CAS  PubMed  CrossRef  Google Scholar 

  24. Nicolaou N, Renkema KY, Bongers EM, Giles RH, Knoers NV. Genetic, environmental, and epigenetic factors involved in CAKUT. Nat Rev Nephrol. 2015;11(12):720–31.

    CAS  PubMed  CrossRef  Google Scholar 

  25. Queisser-Luft A, Stolz G, Wiesel A, Schlaefer K, Spranger J. Malformations in newborn: results based on 30,940 infants and fetuses from the Mainz congenital birth defect monitoring system (1990–1998). Arch Gynecol Obstet. 2002;266(3):163–7.

    CAS  PubMed  CrossRef  Google Scholar 

  26. Chesnaye N, Bonthuis M, Schaefer F, Groothoff JW, Verrina E, Heaf JG, et al. Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry. Pediatr Nephrol. 2014;29(12):2403–10.

    PubMed  CrossRef  Google Scholar 

  27. Wuhl E, van Stralen KJ, Verrina E, Bjerre A, Wanner C, Heaf JG, et al. Timing and outcome of renal replacement therapy in patients with congenital malformations of the kidney and urinary tract. Clin J Am Soc Nephrol. 2013;8(1):67–74.

    PubMed  CrossRef  Google Scholar 

  28. Hoy WE, Bertram JF, Denton RD, Zimanyi M, Samuel T, Hughson MD. Nephron number, glomerular volume, renal disease and hypertension. Curr Opin Nephrol Hypertens. 2008;17(3):258–65.

    PubMed  CrossRef  Google Scholar 

  29. Vivante A, Kohl S, Hwang DY, Dworschak GC, Hildebrandt F. Single-gene causes of congenital anomalies of the kidney and urinary tract (CAKUT) in humans. Pediatr Nephrol. 2014;29(4):695–704.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  30. Cebrian C, Borodo K, Charles N, Herzlinger DA. Morphometric index of the developing murine kidney. Dev Dyn. 2004;231(3):601–8.

    PubMed  CrossRef  Google Scholar 

  31. Saxen L, Sariola H. Early organogenesis of the kidney. Pediatr Nephrol. 1987;1(3):385–92.

    CAS  PubMed  CrossRef  Google Scholar 

  32. Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell. 2010;18(5):698–712.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  33. Pietila I, Vainio SJ. Kidney development: an overview. Nephron Exp Nephrol. 2014;126(2):40.

    PubMed  CrossRef  CAS  Google Scholar 

  34. Schedl A. Renal abnormalities and their developmental origin. Nat Rev Genet. 2007;8(10):791–802.

    CAS  PubMed  CrossRef  Google Scholar 

  35. Schell C, Wanner N, Huber TB. Glomerular development--shaping the multi-cellular filtration unit. Semin Cell Dev Biol. 2014;36:39–49.

    CAS  PubMed  CrossRef  Google Scholar 

  36. Blake J, Rosenblum ND. Renal branching morphogenesis: morphogenetic and signaling mechanisms. Semin Cell Dev Biol. 2014;36:2–12.

    PubMed  CrossRef  Google Scholar 

  37. Cheng HT, Kopan R. The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney. Kidney Int. 2005;68(5):1951–2.

    CAS  PubMed  CrossRef  Google Scholar 

  38. McCright B, Gao X, Shen L, Lozier J, Lan Y, Maguire M, et al. Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development. 2001;128(4):491–502.

    CAS  PubMed  CrossRef  Google Scholar 

  39. Weinmaster G, Roberts VJ, Lemke G. Notch2: a second mammalian Notch gene. Development. 1992;116(4):931–41.

    CAS  PubMed  CrossRef  Google Scholar 

  40. McCright B. Notch signaling in kidney development. Curr Opin Nephrol Hypertens. 2003;12(1):5–10.

    CAS  PubMed  CrossRef  Google Scholar 

  41. Chen L, Al-Awqati Q. Segmental expression of Notch and Hairy genes in nephrogenesis. Am J Physiol Renal Physiol. 2005;288(5):F939–52.

    CAS  PubMed  CrossRef  Google Scholar 

  42. Piscione TD, Wu MY, Quaggin SE. Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis. Gene Expr Patterns. 2004;4(6):707–11.

    CAS  PubMed  CrossRef  Google Scholar 

  43. Cheng HT, Kim M, Valerius MT, Surendran K, Schuster-Gossler K, Gossler A, et al. Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron. Development. 2007;134(4):801–11.

    CAS  PubMed  CrossRef  Google Scholar 

  44. McCright B, Lozier J, Gridley T. A mouse model of Alagille syndrome: Notch2 as a genetic modifier of Jag1 haploinsufficiency. Development. 2002;129(4):1075–82.

    CAS  PubMed  CrossRef  Google Scholar 

  45. Wang P, Pereira FA, Beasley D, Zheng H. Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development. 2003;130(20):5019–29.

    CAS  PubMed  CrossRef  Google Scholar 

  46. Cheng HT, Miner JH, Lin M, Tansey MG, Roth K, Kopan R. Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney. Development. 2003;130(20):5031–42.

    CAS  PubMed  CrossRef  Google Scholar 

  47. Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, et al. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature. 2007;445(7129):776–80.

    PubMed  CrossRef  CAS  Google Scholar 

  48. Fujimura S, Jiang Q, Kobayashi C, Nishinakamura R. Notch2 activation in the embryonic kidney depletes nephron progenitors. J Am Soc Nephrol. 2010;21(5):803–10.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  49. Bonegio RG, Beck LH, Kahlon RK, Lu W, Salant DJ. The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development. Kidney Int. 2011;79(10):1099–112.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  50. Jeong HW, Jeon US, Koo BK, Kim WY, Im SK, Shin J, et al. Inactivation of Notch signaling in the renal collecting duct causes nephrogenic diabetes insipidus in mice. J Clin Invest. 2009;119(11):3290–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Gray MJ, Kim CA, Bertola DR, Arantes PR, Stewart H, Simpson MA, et al. Serpentine fibula polycystic kidney syndrome is part of the phenotypic spectrum of Hajdu-Cheney syndrome. Eur J Hum Genet. 2012;20(1):122–4.

    CAS  PubMed  CrossRef  Google Scholar 

  52. Surendran K, Boyle S, Barak H, Kim M, Stomberski C, McCright B, et al. The contribution of Notch1 to nephron segmentation in the developing kidney is revealed in a sensitized Notch2 background and can be augmented by reducing Mint dosage. Dev Biol. 2010;337(2):386–95.

    CAS  PubMed  CrossRef  Google Scholar 

  53. Niranjan T, Bielesz B, Gruenwald A, Ponda MP, Kopp JB, Thomas DB, et al. The Notch pathway in podocytes plays a role in the development of glomerular disease. Nat Med. 2008;14(3):290–8.

    CAS  PubMed  CrossRef  Google Scholar 

  54. Liu M, Ning X, Li R, Yang Z, Yang X, Sun S, et al. Signalling pathways involved in hypoxia-induced renal fibrosis. J Cell Mol Med. 2017;21(7):1248–59.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  55. Venkatachalam MA, Griffin KA, Lan R, Geng H, Saikumar P, Bidani AK. Acute kidney injury: a springboard for progression in chronic kidney disease. Am J Physiol Renal Physiol. 2010;298(5):F1078–94.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  56. Kobayashi T, Terada Y, Kuwana H, Tanaka H, Okado T, Kuwahara M, et al. Expression and function of the Delta-1/Notch-2/Hes-1 pathway during experimental acute kidney injury. Kidney Int. 2008;73(11):1240–50.

    CAS  PubMed  CrossRef  Google Scholar 

  57. Gupta S, Li S, Abedin MJ, Wang L, Schneider E, Najafian B, et al. Effect of Notch activation on the regenerative response to acute renal failure. Am J Physiol Renal Physiol. 2010;298(1):F209–15.

    CAS  PubMed  CrossRef  Google Scholar 

  58. Murea M, Park JK, Sharma S, Kato H, Gruenwald A, Niranjan T, et al. Expression of Notch pathway proteins correlates with albuminuria, glomerulosclerosis, and renal function. Kidney Int. 2010;78(5):514–22.

    CAS  PubMed  CrossRef  Google Scholar 

  59. Asanuma K, Oliva Trejo JA, Tanaka E. The role of Notch signaling in kidney podocytes. Clin Exp Nephrol. 2017;21(1):1–6.

    CAS  PubMed  CrossRef  Google Scholar 

  60. Walsh DW, Roxburgh SA, McGettigan P, Berthier CC, Higgins DG, Kretzler M, et al. Co-regulation of Gremlin and Notch signalling in diabetic nephropathy. Biochim Biophys Acta. 2008;1782(1):10–21.

    CAS  PubMed  CrossRef  Google Scholar 

  61. Bielesz B, Sirin Y, Si H, Niranjan T, Gruenwald A, Ahn S, et al. Epithelial Notch signaling regulates interstitial fibrosis development in the kidneys of mice and humans. J Clin Invest. 2010;120(11):4040–54.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  62. Sorensen-Zender I, Rong S, Susnik N, Zender S, Pennekamp P, Melk A, et al. Renal tubular Notch signaling triggers a prosenescent state after acute kidney injury. Am J Physiol Renal Physiol. 2014;306(8):F907–15.

    PubMed  CrossRef  CAS  Google Scholar 

  63. Edeling M, Ragi G, Huang S, Pavenstadt H, Susztak K. Developmental signalling pathways in renal fibrosis: the roles of Notch, Wnt and Hedgehog. Nat Rev Nephrol. 2016;12(7):426–39.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  64. Ying Q, Wu G. Molecular mechanisms involved in podocyte EMT and concomitant diabetic kidney diseases: an update. Development. 2017;39(1):474–83.

    Google Scholar 

  65. Niranjan T, Murea M, Susztak K. The pathogenic role of Notch activation in podocytes. Nephron Exp Nephrol. 2009;111(4):e73–9.

    CAS  PubMed  CrossRef  Google Scholar 

  66. Sharma M, Callen S, Zhang D, Singhal PC, Vanden Heuvel GB, Buch S. Activation of Notch signaling pathway in HIV-associated nephropathy. AIDS. 2010;24(14):2161–70.

    CAS  PubMed  CrossRef  Google Scholar 

  67. Lykavieris P, Hadchouel M, Chardot C, Bernard O. Outcome of liver disease in children with Alagille syndrome: a study of 163 patients. Gut. 2001;49(3):431–5.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  68. Habib R, Dommergues JP, Gubler MC, Hadchouel M, Gautier M, Odievre M, et al. Glomerular mesangiolipidosis in Alagille syndrome (arteriohepatic dysplasia). Pediatr Nephrol. 1987;1(3):455–64.

    CAS  PubMed  CrossRef  Google Scholar 

  69. Rosenthal IM, Spellberg MA, McGrew EA, Rozenfeld IH. Absence of interlobular bile ducts. Report of a case of probable intrahepatic bile duct agenesis with severe hypercholesterolemia, xanthomatosis, and glomerular lipid deposition. Am J Dis child. 1961;101:228–37.

    CAS  PubMed  CrossRef  Google Scholar 

  70. Davis J, Griffiths R, Larkin K, Rozansky D, Troxell M. Glomerular basement membrane lipidosis in Alagille syndrome. Pediatr Nephrol. 2010;25(6):1181–4.

    PubMed  CrossRef  Google Scholar 

  71. Benoit G, Sartelet H, Levy E, Boule ME, Alvarez F, Abed L, et al. Mesangiolipidosis in Alagille syndrome--relationship with apolipoprotein A-I. Nephrol Dial Transplant. 2007;22(7):2072–5.

    PubMed  CrossRef  Google Scholar 

  72. Bissonnette MLZ, Lane JC, Chang A. Extreme renal pathology in Alagille syndrome. Kidney Int Rep. 2017;2(3):493–7.

    PubMed  CrossRef  Google Scholar 

  73. Wang H, Wang X, Li Q, Chen S, Liu L, Wei Z, et al. Analysis of JAG1 gene variant in Chinese patients with Alagille syndrome. Gene. 2012;499(1):191–3.

    CAS  PubMed  CrossRef  Google Scholar 

  74. Jurkiewicz D, Gliwicz D, Ciara E, Gerfen J, Pelc M, Piekutowska-Abramczuk D, et al. Spectrum of JAG1 gene mutations in Polish patients with Alagille syndrome. J Appl Genet. 2014;55(3):329–36.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  75. Brennan A, Kesavan A. Novel Heterozygous Mutations in JAG1 and NOTCH2 Genes in a Neonatal Patient with Alagille Syndrome. Case Rep Pediatr. 2017;2017:1368189.

    PubMed  PubMed Central  Google Scholar 

  76. Hannoush ZC, Puerta H, Bauer MS, Goldberg RB. New JAG1 mutation causing Alagille syndrome presenting with severe hypercholesterolemia: case report with emphasis on genetics and lipid abnormalities. J Clin Endocrinol Metab. 2017;102(2):350–3.

    PubMed  Google Scholar 

  77. Jacquet A, Guiochon-Mantel A, Noel LH, Sqalli T, Bedossa P, Hadchouel M, et al. Alagille syndrome in adult patients: it is never too late. Am J Kidney Dis. 2007;49(5):705–9.

    PubMed  CrossRef  Google Scholar 

  78. Berrocal T, Gamo E, Navalon J, Prieto C, Al-Assir I, Cortes P, et al. Syndrome of Alagille: radiological and sonographic findings. A review of 37 cases. Eur Radiol. 1997;7(1):115–8.

    CAS  PubMed  CrossRef  Google Scholar 

  79. Devriendt K, Dooms L, Proesmans W, de Zegher F, Desmet V, Eggermont E. Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: atypical Alagille syndrome? Eur J Pediatr. 1996;155(2):87–90.

    CAS  PubMed  CrossRef  Google Scholar 

  80. Tolia V, Dubois RS, Watts FB Jr, Perrin E. Renal abnormalities in paucity of interlobular bile ducts. J Pediatr Gastroenterol Nutr. 1987;6(6):971–6.

    CAS  PubMed  CrossRef  Google Scholar 

  81. Yucel H, Hoorntje SJ, Bravenboer B. Renal abnormalities in a family with Alagille syndrome. Neth J Med. 2010;68(1):38–9.

    CAS  PubMed  Google Scholar 

  82. Hyams JS, Berman MM, Davis BH. Tubulointerstitial nephropathy associated with arteriohepatic dysplasia. Gastroenterology. 1983;85(2):430–4.

    CAS  PubMed  CrossRef  Google Scholar 

  83. Wolfish NM, Shanon A. Nephropathy in arteriohepatic dysplasia (Alagille's syndrome). Child Nephrol Urol. 1988;9(3):169–72.

    PubMed  Google Scholar 

  84. Hayashi N, Okuyama H, Matsui Y, Yamaya H, Kinoshita E, Minato H, et al. Adult-onset renal failure in a family with Alagille syndrome with proteinuria and a novel JAG1 mutation. Clin Kidney J. 2013;6(3):295–9.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  85. Martin SR, Garel L, Alvarez F. Alagille's syndrome associated with cystic renal disease. Arch Dis Child. 1996;74(3):232–5.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  86. Pombo F, Isla C, Gayol A, Bargiela A. Aortic calcification and renal cysts demonstrated by CT in a teenager with Alagille syndrome. Pediatr Radiol. 1995;25(4):314–5.

    CAS  PubMed  CrossRef  Google Scholar 

  87. Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, et al. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004;109(11):1354–8.

    PubMed  CrossRef  Google Scholar 

  88. Uyttendaele H, Ho J, Rossant J, Kitajewski J. Vascular patterning defects associated with expression of activated Notch4 in embryonic endothelium. Proc Natl Acad Sci U S A. 2001;98(10):5643–8.

    CAS  PubMed  PubMed Central  CrossRef  Google Scholar 

  89. Xue Y, Gao X, Lindsell CE, Norton CR, Chang B, Hicks C, et al. Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet. 1999;8(5):723–30.

    CAS  PubMed  CrossRef  Google Scholar 

  90. Salem JE, Bruguiere E, Iserin L, Guiochon-Mantel A, Plouin PF. Hypertension and aortorenal disease in Alagille syndrome. J Hypertens. 2012;30(7):1300–6.

    CAS  PubMed  CrossRef  Google Scholar 

  91. Kohaut J, Pommier R, Guerin F, Pariente D, Jacquemin E, Martelli H, et al. Abdominal arterial anomalies in children with Alagille syndrome: surgical aspects and outcomes of liver transplantation. J Pediatr Gastroenterol Nutr. 2017;64(6):888–91.

    CAS  PubMed  CrossRef  Google Scholar 

  92. Hirai H, Santo Y, Kogaki S, Kurotobi S, Etani Y, Mushiake S, et al. Successful stenting for renal artery stenosis in a patient with Alagille syndrome. Pediatr Nephrol. 2005;20(6):831–3.

    PubMed  CrossRef  Google Scholar 

  93. Ahn KJ, Yoon JK, Kim GB, Kwon BS, Go JM, Moon JS, et al. Alagille syndrome and a JAG1 mutation: 41 cases of experience at a single center. Korean J Pediatr. 2015;58(10):392–7.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  94. Berard E, Sarles J, Triolo V, Gagnadoux MF, Wernert F, Hadchouel M, et al. Renovascular hypertension and vascular anomalies in Alagille syndrome. Pediatr Nephrol. 1998;12(2):121–4.

    CAS  PubMed  CrossRef  Google Scholar 

  95. Shrivastava R, Williams A, Mikhail A, Roberts D, Richards M, Aithal V. An unusual cause of hypertension and renal failure: a case series of a family with Alagille syndrome. Nephrol Dial Transplant. 2010;25(5):1501–6.

    CAS  PubMed  CrossRef  Google Scholar 

  96. Schonck M, Hoorntje S, van Hooff J. Renal transplantation in Alagille syndrome. Nephrol Dial Transplant. 1998;13(1):197–9.

    CAS  PubMed  CrossRef  Google Scholar 

  97. Schwarzenberg SJ, Grothe RM, Sharp HL, Snover DC, Freese D. Long-term complications of arteriohepatic dysplasia. Am J Med. 1992;93(2):171–6.

    CAS  PubMed  CrossRef  Google Scholar 

  98. Maisonneuve E, Morin F, Crochetiere C, Lemyre E, Bigras JL, Leduc L, et al. Multidisciplinary management of a hepatic and renal transplant patient with Alagille syndrome. Int J Obstet Anesth. 2012;21(4):382–3.

    CAS  PubMed  CrossRef  Google Scholar 

  99. Kamath BM, Yin W, Miller H, Anand R, Rand EB, Alonso E, et al. Outcomes of liver transplantation for patients with Alagille syndrome: the studies of pediatric liver transplantation experience. Liver Transplant. 2012;18(8):940–8.

    CrossRef  Google Scholar 

  100. Arnon R, Annunziato R, Miloh T, Suchy F, Sakworawich A, Sogawa H, et al. Orthotopic liver transplantation for children with Alagille syndrome. Pediatr Transplant. 2010;14(5):622–8.

    PubMed  CrossRef  Google Scholar 

  101. Squires RH, Ng V, Romero R, Ekong U, Hardikar W, Emre S, et al. Evaluation of the pediatric patient for liver transplantation: 2014 practice guideline by the American Association for the Study of Liver Diseases, American Society of Transplantation and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Hepatology. J Pediatr Gastroenterol Nutr. 2014;60(1):362–98.

    Google Scholar 

  102. Kelly DA, Bucuvalas JC, Alonso EM, Karpen SJ, Allen U, Green M, et al. Long-term medical management of the pediatric patient after liver transplantation: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transplant. 2013;19(8):798–825.

    CrossRef  Google Scholar 

  103. Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;50(6):580–6.

    PubMed  CrossRef  Google Scholar 

  104. Kamath BM, Munoz PS, Bab N, Baker A, Chen Z, Spinner NB, et al. A longitudinal study to identify laboratory predictors of liver disease outcome in Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;50(5):526–30.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  105. Mouzaki M, Bass LM, Sokol RJ, Piccoli DA, Quammie C, Loomes KM, et al. Early life predictive markers of liver disease outcome in an International, Multicentre Cohort of children with Alagille syndrome. Liver Int. 2016;36(5):755–60.

    PubMed  CrossRef  Google Scholar 

  106. Elisofon SA, Emerick KM, Sinacore JM, Alonso EM. Health status of patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010;51(6):759–65.

    PubMed  CrossRef  Google Scholar 

  107. Kamath BM, Chen Z, Romero R, Fredericks EM, Alonso EM, Arnon R, et al. Quality of Life and Its Determinants in a Multicenter Cohort of Children with Alagille Syndrome. The Journal of pediatrics. 2015;167(2):390–6.e3.

    PubMed  PubMed Central  CrossRef  Google Scholar 

  108. Wang JS, Wang XH, Zhu QR, Wang ZL, Hu XQ, Zheng S. Clinical and pathological characteristics of Alagille syndrome in Chinese children. World J Pediatr. 2008;4(4):283–8.

    CAS  PubMed  CrossRef  Google Scholar 

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Romero, R. (2018). The Renal Sequelae of Alagille Syndrome as a Product of Altered Notch Signaling During Kidney Development. In: Kamath, B., Loomes, K. (eds) Alagille Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-319-94571-2_8

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