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Next-Generation Sequencing in Paediatric Hepatology

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Pediatric Hepatology and Liver Transplantation

Abstract

Nearly half of children with chronic liver disorders have a genetic cause, and approximately 20% of paediatric liver transplants are performed in children with monogenic diseases (MDs). In the field of inherited disorders, next-generation sequencing (NGS) has already revolutionized the analysis of human genetic variations, demonstrating to be a great tool to improve the diagnostic yield and offering a highly cost-effective way to diagnose MDs. Among the NGS strategies, the use of targeted gene panels has proven useful to rapidly and reliably confirm a clinical suspicion, whereas the whole exome sequencing (WES) with variants filtering has been adopted to assist the diagnosis in unclear clinical scenarios. WES is powerful but challenging, since it detects a great number of variants of unknown significance that can be misinterpreted and lead to wrong diagnosis. In paediatric hepatology, targeted panels can be very valuable to discriminate neonatal/infantile cholestatic disorders, disclose genetic causes of acute liver failure and diagnose the subtype of inborn errors of metabolism presenting with a similar phenotype (such as glycogen storage disorders, mitochondrial cytopathies or non-alcoholic fatty liver).

The inevitable inclusion of NGS in diagnostic algorithms will soon lead to a new era in medicine, changing completely our approach to the patient as well as our understanding of factors affecting genotype-phenotype match. In this chapter, we discuss the opportunities and the challenges offered nowadays by NGS, which will become a pivotal tool for the diagnosis of liver-based MDs.

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References

  1. Antonarakis SE, Beckmann JS. Mendelian disorders deserve more attention. Nat Rev Genet. 2006;7(4):277–82.

    Article  CAS  PubMed  Google Scholar 

  2. Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977;74(12):5463–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11(1):31–46.

    Article  CAS  PubMed  Google Scholar 

  4. Stranneheim H, Wedell A. Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders. J Intern Med. 2016;279(1):3–15. Epub 2015/08/08.

    Article  CAS  PubMed  Google Scholar 

  5. Kuhlenbaumer G, Hullmann J, Appenzeller S. Novel genomic techniques open new avenues in the analysis of monogenic disorders. Hum Mutat. 2011;32(2):144–51. Epub 2011/02/01.

    Article  PubMed  Google Scholar 

  6. Bush WS, Oetjens MT, Crawford DC. Unravelling the human genome-phenome relationship using phenome-wide association studies. Nat Rev Genet. 2016;17(3):129–45.

    Article  CAS  PubMed  Google Scholar 

  7. Mann DA. Epigenetics in liver disease. Hepatology. 2014;60(4):1418–25.

    Article  CAS  PubMed  Google Scholar 

  8. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68.

    Article  CAS  PubMed  Google Scholar 

  9. Szelinger S, Malenica I, Corneveaux JJ, Siniard AL, Kurdoglu AA, Ramsey KM, et al. Characterization of X chromosome inactivation using integrated analysis of whole-exome and mRNA sequencing. PLoS One. 2014;9(12):e113036. Epub 2014/12/17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Nicastro E, Loudianos G, Zancan L, D’Antiga L, Maggiore G, Marcellini M, et al. Genotype-phenotype correlation in Italian children with Wilson’s disease. J Hepatol. 2009;50(3):555–61. Epub 2009/01/03.

    Article  CAS  PubMed  Google Scholar 

  11. Sze YK, Dhawan A, Taylor RM, Bansal S, Mieli-Vergani G, Rela M, et al. Pediatric liver transplantation for metabolic liver disease: experience at King’s College Hospital. Transplantation. 2009;87(1):87–93.

    Article  PubMed  Google Scholar 

  12. Nicastro E, D’Antiga L. Next generation sequencing in pediatric hepatology and liver transplantation. Liver Transpl. 2018;24(2):282–93. Epub 2017/10/29.

    Article  PubMed  Google Scholar 

  13. Couderc R, Jonard L, Louha M. Next generation sequencing: the technology we need in pediatric laboratories? Clin Biochem. 2011;44(7):514–5. Epub 2011/11/01.

    Article  PubMed  Google Scholar 

  14. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, et al. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013;15(9):733–47.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Rizzo JM, Buck MJ. Key principles and clinical applications of “next-generation” DNA sequencing. Cancer Prev Res. 2012;5(7):887–900.

    Article  CAS  Google Scholar 

  16. Kingsmore SF, Saunders CJ. Deep sequencing of patient genomes for disease diagnosis: when will it become routine? Sci Transl Med. 2011;3(87):87ps23.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Brookes AJ, Robinson PN. Human genotype-phenotype databases: aims, challenges and opportunities. Nat Rev Genet. 2015;16(12):702–15.

    Article  CAS  PubMed  Google Scholar 

  18. Christenhusz GM, Devriendt K, Van Esch H, Dierickx K. Focus group discussions on secondary variants and next-generation sequencing technologies. Eur J Med Genet. 2015;58(4):249–57. Epub 2015/02/11.

    Article  PubMed  Google Scholar 

  19. Casanova J-L, Conley ME, Seligman SJ, Abel L, Notarangelo LD. Guidelines for genetic studies in single patients: lessons from primary immunodeficiencies. J Exp Med. 2014;211(11):2137–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ng SB, Nickerson DA, Bamshad MJ, Shendure J. Massively parallel sequencing and rare disease. Hum Mol Genet. 2010;19(R2):R119–R24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang J, Cui H, Lee NC, Hwu WL, Chien YH, Craigen WJ, et al. Clinical application of massively parallel sequencing in the molecular diagnosis of glycogen storage diseases of genetically heterogeneous origin. Genet Med. 2013;15(2):106–14. Epub 2012/08/18.

    Article  CAS  PubMed  Google Scholar 

  22. Togawa T, Sugiura T, Ito K, Endo T, Aoyama K, Ohashi K, et al. Molecular genetic dissection and neonatal/infantile intrahepatic cholestasis using targeted next-generation sequencing. J Pediatr. 2016;171:171–7.e1–4. Epub 2016/02/10.

    Article  PubMed  Google Scholar 

  23. McKiernan P, Ball S, Santra S, Foster K, Fratter C, Poulton J, et al. Incidence of primary mitochondrial disease in children younger than 2 years presenting with acute liver failure. J Pediatr Gastroenterol Nutr. 2016;63(6):592–7. Epub 2016/08/03.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ravi Kanth VV, Sasikala M, Sharma M, Rao PN, Reddy DN. Genetics of non-alcoholic fatty liver disease: from susceptibility and nutrient interactions to management. World J Hepatol. 2016;8(20):827–37.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jones MA, Rhodenizer D, da Silva C, Huff IJ, Keong L, Bean LJ, et al. Molecular diagnostic testing for congenital disorders of glycosylation (CDG): detection rate for single gene testing and next generation sequencing panel testing. Mol Genet Metab. 2013;110(1–2):78–85. Epub 2013/06/29.

    Article  CAS  PubMed  Google Scholar 

  26. Sakai R, Sifrim A, Vande Moere A, Aerts J. TrioVis: a visualization approach for filtering genomic variants of parent-child trios. Bioinformatics. 2013;29(14):1801–2. Epub 2013/05/10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rabbani B, Mahdieh N, Hosomichi K, Nakaoka H, Inoue I. Next-generation sequencing: impact of exome sequencing in characterizing Mendelian disorders. J Hum Genet. 2012;57(10):621–32.

    Article  CAS  PubMed  Google Scholar 

  28. Bamshad MJ, Ng SB, Bigham AW, Tabor HK, Emond MJ, Nickerson DA, et al. Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet. 2011;12(11):745–55.

    Article  CAS  PubMed  Google Scholar 

  29. Sulonen A-M, Ellonen P, Almusa H, Lepistö M, Eldfors S, Hannula S, et al. Comparison of solution-based exome capture methods for next generation sequencing. Genome Biol. 2011;12(9):1–18.

    Article  CAS  Google Scholar 

  30. Niroula A, Vihinen M. Variation interpretation predictors: principles, types, performance and choice. Hum Mutat. 2016;37(6):579–97. Epub 2016/03/19.

    Article  PubMed  Google Scholar 

  31. Jarinova O, Ekker M. Regulatory variations in the era of next-generation sequencing: implications for clinical molecular diagnostics. Hum Mutat. 2012;33(7):1021–30. Epub 2012/03/21.

    Article  CAS  PubMed  Google Scholar 

  32. Belkadi A, Bolze A, Itan Y, Cobat A, Vincent QB, Antipenko A, et al. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc Natl Acad Sci U S A. 2015;112(17):5473–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lemke AA, Bick D, Dimmock D, Simpson P, Veith R. Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study. Clin Genet. 2013;84(3):230–6. Epub 2012/11/21.

    Article  CAS  PubMed  Google Scholar 

  34. Derkach A, Chiang T, Gong J, Addis L, Dobbins S, Tomlinson I, et al. Association analysis using next-generation sequence data from publicly available control groups: the robust variance score statistic. Bioinformatics. 2014;30(15):2179–88. Epub 2014/04/16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Matthijs G, Souche E, Alders M, Corveleyn A, Eck S, Feenstra I, et al. Guidelines for diagnostic next-generation sequencing. Eur J Hum Genet. 2016;24(1):2–5.

    Article  CAS  PubMed  Google Scholar 

  36. May T, Zusevics KL, Strong KA. On the ethics of clinical whole genome sequencing of children. Pediatrics. 2013;132(2):207–9. Epub 2013/07/10.

    Article  PubMed  Google Scholar 

  37. Fagiuoli S, Daina E, D’Antiga L, Colledan M, Remuzzi G. Monogenic diseases that can be cured by liver transplantation. J Hepatol. 2013;59(3):595–612. Epub 2013/04/13.

    Article  PubMed  Google Scholar 

  38. Blok MJ, van den Bosch BJ, Jongen E, Hendrickx A, de Die-Smulders CE, Hoogendijk JE, et al. The unfolding clinical spectrum of POLG mutations. J Med Genet. 2009;46(11):776–85.

    Article  CAS  PubMed  Google Scholar 

  39. Sallie R, Katsiyiannakis L, Baldwin D, Davies S, O’Grady J, Mowat A, et al. Failure of simple biochemical indexes to reliably differentiate fulminant Wilson’s disease from other causes of fulminant liver failure. Hepatology. 1992;16(5):1206–11. Epub 1992/11/01

    Article  CAS  PubMed  Google Scholar 

  40. Fawaz R, Baumann U, Ekong U, Fischler B, Hadzic N, Mack CL, et al. Guideline for the evaluation of cholestatic jaundice in infants: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2017;64(1):154–68. Epub 2016/07/19.

    Article  CAS  PubMed  Google Scholar 

  41. Balistreri WF, Bezerra JA. Whatever happened to “neonatal hepatitis”? Clin Liver Dis. 2006;10(1):27–53.

    Article  PubMed  Google Scholar 

  42. Grammatikopoulos T, Sambrotta M, Strautnieks S, Foskett P, Knisely AS, Wagner B, et al. Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis. J Hepatol. 2016;65(6):1179–87. Epub 2016/07/30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Balistreri WF, Bezerra JA, Jansen P, Karpen SJ, Shneider BL, Suchy FJ. Intrahepatic cholestasis: summary of an American Association for the Study of Liver Diseases single-topic conference. Hepatology. 2005;42(1):222–35. Epub 2005/05/18.

    Article  PubMed  Google Scholar 

  44. Lu F-T, Wu J-F, Hsu H-Y, Ni Y-H, Chang M-H, Chao C-I, et al. γ-Glutamyl transpeptidase level as a screening marker among diverse etiologies of infantile intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. 2014;59(6):695–701.

    Article  CAS  PubMed  Google Scholar 

  45. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. 2009;4(1):1–12.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sambrotta M, Strautnieks S, Papouli E, Rushton P, Clark BE, Parry DA, et al. Mutations in TJP2 cause progressive cholestatic liver disease. Nat Genet. 2014;46(4):326–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Setchell KDR, Heubi JE, Shah S, Lavine JE, Suskind D, Al–Edreesi M, et al. Genetic defects in bile acid conjugation cause fat-soluble vitamin deficiency. Gastroenterology. 2013;144(5):945–55.e6.

    Article  CAS  PubMed  Google Scholar 

  48. Riello L, D’Antiga L, Guido M, Alaggio R, Giordano G, Zancan L. Titration of bile acid supplements in 3beta-hydroxy-Delta 5-C27-steroid dehydrogenase/isomerase deficiency. J Pediatr Gastroenterol Nutr. 2010;50(6):655–60. Epub 2010/04/20.

    Article  CAS  PubMed  Google Scholar 

  49. Droge C, Bonus M, Baumann U, Klindt C, Lainka E, Kathemann S, et al. Sequencing of FIC1, BSEP and MDR3 in a large cohort of patients with cholestasis revealed a high number of different genetic variants. J Hepatol. 2017;67(6):1253–64. Epub 2017/07/25

    Article  PubMed  CAS  Google Scholar 

  50. Gomez-Ospina N, Potter CJ, Xiao R, Manickam K, Kim MS, Kim KH, et al. Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis. Nat Commun. 2016;7:10713. Epub 2016/02/19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Qiu YL, Gong JY, Feng JY, Wang RX, Han J, Liu T, et al. Defects in myosin VB are associated with a spectrum of previously undiagnosed low gamma-glutamyltransferase cholestasis. Hepatology. 2017;65(5):1655–69. Epub 2016/12/28.

    Article  CAS  PubMed  Google Scholar 

  52. Knisely AS, Strautnieks SS, Meier Y, Stieger B, Byrne JA, Portmann BC, et al. Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology. 2006;44:478–86.

    Article  CAS  PubMed  Google Scholar 

  53. Iannelli F, Collino A, Sinha S, Radaelli E, Nicoli P, D’Antiga L, et al. Massive gene amplification drives paediatric hepatocellular carcinoma caused by bile salt export pump deficiency. Nat Commun. 2014;5:3850. Epub 2014/05/14.

    Article  CAS  PubMed  Google Scholar 

  54. Nicastro E, Stephenne X, Smets F, Fusaro F, de Magnee C, Reding R, et al. Recovery of graft steatosis and protein-losing enteropathy after biliary diversion in a PFIC 1 liver transplanted child. Pediatr Transplant. 2012;16(5):E177–82. Epub 2011/06/16.

    Article  PubMed  Google Scholar 

  55. Jara P, Hierro L, Martínez-Fernández P, Alvarez-Doforno R, Yánez F, Diaz MC, et al. Recurrence of bile salt export pump deficiency after liver transplantation. N Engl J Med. 2009;361(14):1359–67.

    Article  CAS  PubMed  Google Scholar 

  56. Shneider BL. Liver transplantation for progressive familial intrahepatic cholestasis: the evolving role of genotyping. Liver Transpl. 2009;15(6):565–6.

    Article  PubMed  Google Scholar 

  57. Hadzic N, Bull LN, Clayton PT, Knisely AS. Diagnosis in bile acid-CoA: amino acid N-acyltransferase deficiency. World J Gastroenterol. 2012;18(25):3322–6. Epub 2012/07/12.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Chen S-T, Su Y-N, Ni Y-H, Hwu W-L, Lee N-C, Chien Y-H, et al. Diagnosis of neonatal intrahepatic cholestasis caused by citrin deficiency using high-resolution melting analysis and a clinical scoring system. J Pediatr. 2012;161(4):626–31.e2.

    Article  CAS  PubMed  Google Scholar 

  59. Herbst SM, Schirmer S, Posovszky C, Jochum F, Rödl T, Schroeder JA, et al. Taking the next step forward—diagnosing inherited infantile cholestatic disorders with next generation sequencing. Mol Cell Probes. 2015;29(5):291–8.

    Article  CAS  PubMed  Google Scholar 

  60. Alagille D, Odievre M, Gautier M, Dommergues JP. Hepatic ductular hypoplasia associated with characteristic facies, vertebral malformations, retarded physical, mental, and sexual development, and cardiac murmur. J Pediatr. 1975;86(1):63–71. Epub 1975/01/01.

    Article  CAS  PubMed  Google Scholar 

  61. Li L, Dong J, Wang X, Guo H, Wang H, Zhao J, et al. JAG1 mutation spectrum and origin in Chinese children with clinical features of Alagille syndrome. PLoS One. 2015;10(6):e0130355. Epub 2015/06/16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Emerick KM, Krantz ID, Kamath BM, Darling C, Burrowes DM, Spinner NB, et al. Intracranial vascular abnormalities in patients with Alagille syndrome. J Pediatr Gastroenterol Nutr. 2005;41(1):99–107. Epub 2005/07/02.

    Article  PubMed  Google Scholar 

  63. McKiernan PJ. Neonatal cholestasis. Semin Neonatol. 2002;7(2):153–65.

    Article  CAS  PubMed  Google Scholar 

  64. Yerushalmi B, Sokol RJ, Narkewicz MR, Smith D, Ashmead JW, Wenger DA. Niemann-pick disease type C in neonatal cholestasis at a North American Center. J Pediatr Gastroenterol Nutr. 2002;35(1):44–50.

    Article  PubMed  Google Scholar 

  65. Gotti G, Marseglia A, De Giacomo C, Iascone M, Sonzogni A, D’Antiga L. Neonatal jaundice with splenomegaly: not a common pick. Fetal Pediatr Pathol. 2016;35(2):108–11. Epub 2016/02/06.

    Article  PubMed  Google Scholar 

  66. Lang T, Muhlbauer M, Strobelt M, Weidinger S, Hadorn HB. Alpha-1-antitrypsin deficiency in children: liver disease is not reflected by low serum levels of alpha-1-antitrypsin—a study on 48 pediatric patients. Eur J Med Res. 2005;10(12):509–14. Epub 2005/12/17.

    CAS  PubMed  Google Scholar 

  67. Snyder MR, Katzmann JA, Butz ML, Wiley C, Yang P, Dawson DB, et al. Diagnosis of alpha-1-antitrypsin deficiency: an algorithm of quantification, genotyping, and phenotyping. Clin Chem. 2006;52(12):2236–42. Epub 2006/10/21

    Article  CAS  PubMed  Google Scholar 

  68. Squires RH Jr, Shneider BL, Bucuvalas J, Alonso E, Sokol RJ, Narkewicz MR, et al. Acute liver failure in children: the first 348 patients in the pediatric acute liver failure study group. J Pediatr. 2006;148(5):652–8.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Hegarty R, Hadzic N, Gissen P, Dhawan A. Inherited metabolic disorders presenting as acute liver failure in newborns and young children: King’s College Hospital experience. Eur J Pediatr. 2015;174(10):1387–92.

    Article  CAS  PubMed  Google Scholar 

  70. Gallagher RC, Lam C, Wong D, Cederbaum S, Sokol RJ. Significant hepatic involvement in patients with ornithine transcarbamylase deficiency. J Pediatr. 2014;164(4):720–5 e6. Epub 2014/02/04.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Staufner C, Haack TB, Kopke MG, Straub BK, Kolker S, Thiel C, et al. Recurrent acute liver failure due to NBAS deficiency: phenotypic spectrum, disease mechanisms, and therapeutic concepts. J Inherit Metab Dis. 2016;39(1):3–16. Epub 2015/11/07.

    Article  CAS  PubMed  Google Scholar 

  72. Cui H, Li F, Chen D, Wang G, Truong CK, Enns GM, et al. Comprehensive next-generation sequence analyses of the entire mitochondrial genome reveal new insights into the molecular diagnosis of mitochondrial DNA disorders. Genet Med. 2013;15(5):388–94. Epub 2013/01/05.

    Article  CAS  PubMed  Google Scholar 

  73. Dames S, Chou LS, Xiao Y, Wayman T, Stocks J, Singleton M, et al. The development of next-generation sequencing assays for the mitochondrial genome and 108 nuclear genes associated with mitochondrial disorders. J Mol Diagn. 2013;15(4):526–34. Epub 2013/05/15.

    Article  CAS  PubMed  Google Scholar 

  74. Spinazzola A, Invernizzi F, Carrara F, Lamantea E, Donati A, DiRocco M, et al. Clinical and molecular features of mitochondrial DNA depletion syndromes. J Inherit Metab Dis. 2008;32(2):143–58.

    Article  PubMed  CAS  Google Scholar 

  75. Menezes MJ, Riley LG, Christodoulou J. Mitochondrial respiratory chain disorders in childhood: Insights into diagnosis and management in the new era of genomic medicine. Biochim Biophys Acta Gen Subj. 2014;1840(4):1368–79.

    Article  CAS  Google Scholar 

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    Lorenzo D’Antiga

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    Lorenzo D'Antiga

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D’Antiga, L. (2019). Next-Generation Sequencing in Paediatric Hepatology. In: D'Antiga, L. (eds) Pediatric Hepatology and Liver Transplantation. Springer, Cham. https://doi.org/10.1007/978-3-319-96400-3_42

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