The Role of Genome Sequencing in Neonatal Intensive Care Units

Literature Cited

1. 1.

   Almli LM, Ely DM, Ailes EC, Abouk R, Grosse SD et al. 2020. Infant mortality attributable to birth defects—United States, 2003–2017. Morb. Mortal. Wkly. Rep. 69:25–29
   [Google Scholar]
2. 2.

   Aust. Genom. Health Alliance Acute Care Flagship. 2020. Feasibility of ultra-rapid exome sequencing in critically ill infants and children with suspected monogenic conditions in the Australian public health care system. JAMA 323:2503–11
   [Google Scholar]
3. 3.

   Bainbridge MN, Wiszniewski W, Murdock DR, Friedman J, Gonzaga-Jauregui C et al. 2011. Whole-genome sequencing for optimized patient management. Sci. Transl. Med. 3:87re3
   [Google Scholar]
4. 4.

   Bauer MS, Damschroder L, Hagedorn H, Smith J, Kilbourne AM. 2015. An introduction to implementation science for the non-specialist. BMC Psychol 3:32
   [Google Scholar]
5. 5.

   Bayat A, Bayat M, Rubboli G, Moller RS. 2021. Epilepsy syndromes in the first year of life and usefulness of genetic testing for precision therapy. Genes 12:1051
   [Google Scholar]
6. 6.

   Bell CJ, Dinwiddie DL, Miller NA, Hateley SL, Ganusova EE et al. 2011. Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci. Transl. Med. 3:65ra4
   [Google Scholar]
7. 7.

   Berry SA. 2015. Newborn screening. Clin. Perinatol. 42:441–53
   [Google Scholar]
8. 8.

   Biesecker LG, Green ED, Manolio T, Solomon BD, Curtis D 2021. Should all babies have their genome sequenced at birth?. BMJ 375:n2679
   [Google Scholar]
9. 9.

   Blue Shield Calif. 2019. Whole exome and whole genome sequencing for diagnosis of genetic disorders Med. Policy Doc., Blue Shield Calif. Oakland, CA:
10. 10.

    Brynn L 2018. Prenatal Diagnosis Methods Mol. Biol. 1885 New York: Humana . , 2nd ed..
11. 11.

    Cakici JA, Dimmock DP, Caylor SA, Gaughran M, Clarke C et al. 2020. A prospective study of parental perceptions of rapid whole-genome and -exome sequencing among seriously ill infants. Am. J. Hum. Genet. 107:953–62
    [Google Scholar]
12. 12.

    Carey AS, Schacht JP, Umandap C, Fasel D, Weng C et al. 2020. Rapid exome sequencing in PICU patients with new-onset metabolic or neurological disorders. Pediatr. Res. 88:761–68
    [Google Scholar]
13. 13.

    Chambers DA, Feero WG, Khoury MJ. 2016. Convergence of implementation science, precision medicine, and the learning health care system: a new model for biomedical research. JAMA 315:1941–42
    [Google Scholar]
14. 14.

    Choi M, Scholl UI, Ji W, Liu T, Tikhonova IR et al. 2009. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. PNAS 106:19096–101
    [Google Scholar]
15. 15.

    Chung CCY, Leung GKC, Mak CCY, Fung JLF, Lee M et al. 2020. Rapid whole-exome sequencing facilitates precision medicine in paediatric rare disease patients and reduces healthcare costs. Lancet Reg. Health West Pac. 1:100001
    [Google Scholar]
16. 16.

    Clark MM, Hildreth A, Batalov S, Ding Y, Chowdhury S et al. 2019. Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation. Sci. Transl. Med. 11:eaat6177
    [Google Scholar]
17. 17.

    Clark MM, Stark Z, Farnaes L, Tan TY, White SM et al. 2018. Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases. NPJ Genom. Med. 3:16
    [Google Scholar]
18. 18.

    Comm. Genet., Soc. Matern.-Fetal Med 2016. Committee Opinion No. 682: microarrays and next-generation sequencing technology: the use of advanced genetic diagnostic tools in obstetrics and gynecology. Obstet. Gynecol. 128:e262–68
    [Google Scholar]
19. 19.

    Conley ME, Dobbs AK, Farmer DM, Kilic S, Paris K et al. 2009. Primary B cell immunodeficiencies: comparisons and contrasts. Annu. Rev. Immunol. 27:199–227
    [Google Scholar]
20. 20.

    De La Vega FM, Chowdhury S, Moore B, Frise E, McCarthy J et al. 2021. Artificial intelligence enables comprehensive genome interpretation and nomination of candidate diagnoses for rare genetic diseases. Genome Med 13:153
    [Google Scholar]
21. 21.

    Denommé-Pichon AS, Vitobello A, Olaso R, Ziegler A, Jeanne M et al. 2022. Accelerated genome sequencing with controlled costs for infants in intensive care units: a feasibility study in a French hospital network. Eur. J. Hum. Genet. 30:567–76
    [Google Scholar]
22. 22.

    Dimmock DP, Caylor S, Waldman B, Benson W, Ashburner C et al. 2021. Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children's hospitals demonstrates improved clinical outcomes and reduced costs of care. Am. J. Hum. Genet. 108:1231–38
    [Google Scholar]
23. 23.

    Dimmock DP, Clark MM, Gaughran M, Cakici JA, Caylor SA et al. 2020. An RCT of rapid genomic sequencing among seriously ill infants results in high clinical utility, changes in management, and low perceived harm. Am. J. Hum. Genet. 107:942–52
    [Google Scholar]
24. 24.

    Elliott AM, du Souich C, Lehman A, Guella I, Evans DM et al. 2019. RAPIDOMICS: rapid genome-wide sequencing in a neonatal intensive care unit—successes and challenges. Eur. J. Pediatr. 178:1207–18
    [Google Scholar]
25. 25.

    Farnaes L, Hildreth A, Sweeney NM, Clark MM, Chowdhury S et al. 2018. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization. NPJ Genom. Med. 3:10
    [Google Scholar]
26. 26.

    Franck LS, Kriz RM, Rego S, Garman K, Hobbs C, Dimmock D. 2021. Implementing rapid whole-genome sequencing in critical care: a qualitative study of facilitators and barriers to new technology adoption. J. Pediatr. 237:237–43.e2
    [Google Scholar]
27. 27.

    Freed AS, Clowes Candadai SV, Sikes MC, Thies J, Byers HM et al. 2020. The impact of rapid exome sequencing on medical management of critically ill children. J. Pediatr. 226:202–12.e1
    [Google Scholar]
28. 28.

    French CE, Delon I, Dolling H, Sanchis-Juan A, Shamardina O et al. 2019. Whole genome sequencing reveals that genetic conditions are frequent in intensively ill children. Intensive Care Med 45:627–36
    [Google Scholar]
29. 29.

    Fridriksdottir R, Jonsson AJ, Jensson BO, Sverrisson KO, Arnadottir GA et al. 2021. Sequence variants in malignant hyperthermia genes in Iceland: classification and actionable findings in a population database. Eur. J. Hum. Genet. 29:1819–24
    [Google Scholar]
30. 30.

    Goodman DC, Little GA, Harrison WN, Moen A, Mowitz ME et al., eds. 2019. The Dartmouth Atlas of Neonatal Intensive Care Lebanon, NH: Dartmouth Inst. Health Policy Clin. Pract.
31. 31.

    Gubbels CS, VanNoy GE, Madden JA, Copenheaver D, Yang S et al. 2020. Prospective, phenotype-driven selection of critically ill neonates for rapid exome sequencing is associated with high diagnostic yield. Genet. Med. 22:736–44
    [Google Scholar]
32. 32.

    Hagadorn JI, Johnson KR, Hill D, Sink DW. 2020. Improving the quality of quality metrics in neonatology. Semin. Perinatol. 44:151244
    [Google Scholar]
33. 33.

    Harrison W, Goodman D. 2015. Epidemiologic trends in neonatal intensive care, 2007–2012. JAMA Pediatr 169:855–62
    [Google Scholar]
34. 34.

    Hays T, Wapner RJ. 2021. Genetic testing for unexplained perinatal disorders. Curr. Opin. Pediatr. 33:195–202
    [Google Scholar]
35. 35.

    Heron M. 2021. Deaths: leading causes for 2019 Natl. Vital Stat. Rep. 70(9) Natl. Cent. Health Stat. Hyattsville, MD:
36. 36.

    Inst. Med. 2015. Genomics-Enabled Learning Health Care Systems: Gathering and Using Genomic Information to Improve Patient Care and Research Washington, DC: Natl. Acad. Press
37. 37.

    Ioannidis AG, Blanco-Portillo J, Sandoval K, Hagelberg E, Barberena-Jonas C et al. 2021. Paths and timings of the peopling of Polynesia inferred from genomic networks. Nature 597:522–26
    [Google Scholar]
38. 38.

    Jensen K, Murray F. 2005. Intellectual property landscape of the human genome. Science 310:239–40
    [Google Scholar]
39. 39.

    Johns Hopkins Univ. 2022. OMIM gene map statistics. Online Mendelian Inheritance in Man https://www.omim.org/statistics/geneMap
    [Google Scholar]
40. 40.

    Katsanis N. 2016. The continuum of causality in human genetic disorders. Genome Biol 17:233
    [Google Scholar]
41. 41.

    Kilby MD. 2021. The role of next-generation sequencing in the investigation of ultrasound-identified fetal structural anomalies. BJOG 128:420–29
    [Google Scholar]
42. 42.

    Kim JI, Ju YS, Park H, Kim S, Lee S et al. 2009. A highly annotated whole-genome sequence of a Korean individual. Nature 460:1011–15
    [Google Scholar]
43. 43.

    Kingsmore SF, Cakici JA, Clark MM, Gaughran M, Feddock M et al. 2019. A randomized, controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants. Am. J. Hum. Genet. 105:719–33
    [Google Scholar]
44. 44.

    Kingsmore SF, Henderson A, Owen MJ, Clark MM, Hansen C et al. 2020. Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing. NPJ Genom. Med. 5:49
    [Google Scholar]
45. 45.

    Kingsmore SF, Ramchandar N, James K, Niemi AK, Feigenbaum A et al. 2020. Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system. Cold Spring Harb. Mol. Case Stud. 6:a004705
    [Google Scholar]
46. 46.

    Kingsmore SF, Saunders CJ. 2011. Deep sequencing of patient genomes for disease diagnosis: When will it become routine?. Sci. Transl. Med. 3:87ps23
    [Google Scholar]
47. 47.

    Kitagawa H, Pringle KC. 2017. Fetal surgery: a critical review. Pediatr. Surg. Int. 33:421–33
    [Google Scholar]
48. 48.

    Kong A, Frigge ML, Masson G, Besenbacher S, Sulem P et al. 2012. Rate of de novo mutations and the importance of father's age to disease risk. Nature 488:471–75
    [Google Scholar]
49. 49.

    Kosova G, Abney M, Ober C. 2010. Heritability of reproductive fitness traits in a human population. PNAS 107:Suppl. 11772–78
    [Google Scholar]
50. 50.

    Krstic N, Obican SG. 2020. Current landscape of prenatal genetic screening and testing. Birth Defects Res 112:321–31
    [Google Scholar]
51. 51.

    Lee H, Huang AY, Wang LK, Yoon AJ, Renteria G et al. 2020. Diagnostic utility of transcriptome sequencing for rare Mendelian diseases. Genet. Med. 22:490–99
    [Google Scholar]
52. 52.

    Lee JS, Yoo T, Lee M, Lee Y, Jeon E et al. 2020. Genetic heterogeneity in Leigh syndrome: highlighting treatable and novel genetic causes. Clin. Genet. 97:586–94
    [Google Scholar]
53. 53.

    Levy S, Sutton G, Ng PC, Feuk L, Halpern AL et al. 2007. The diploid genome sequence of an individual human. PLOS Biol 5:e254
    [Google Scholar]
54. 54.

    Lialiaris T, Mantadakis E, Kareli D, Mpountoukas P, Tsalkidis A, Chatzimichail A. 2010. Frequency of genetic diseases and health coverage of children requiring admission in a general pediatric clinic of northern Greece. Ital. J. Pediatr. 36:9
    [Google Scholar]
55. 55.

    Malfait F, Castori M, Francomano CA, Giunta C, Kosho T, Byers PH. 2020. The Ehlers-Danlos syndromes. Nat. Rev. Dis. Primers 6:64
    [Google Scholar]
56. 56.

    Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM et al. 2021. Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 23:2029–37
    [Google Scholar]
57. 57.

    Margulies M, Egholm M, Altman WE, Attiya S, Bader JS et al. 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437:376–80
    [Google Scholar]
58. 58.

    Maron JL, Kingsmore SF, Wigby K, Chowdhury S, Dimmock D et al. 2021. Novel variant findings and challenges associated with the clinical integration of genomic testing: an interim report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) study. JAMA Pediatr 175:e205906
    [Google Scholar]
59. 59.

    McCandless SE, Brunger JW, Cassidy SB. 2004. The burden of genetic disease on inpatient care in a children's hospital. Am. J. Hum. Genet. 74:121–27
    [Google Scholar]
60. 60.

    McGinnis JM, Fineberg HV, Dzau VJ. 2021. Advancing the learning health system. N. Engl. J. Med. 385:1–5
    [Google Scholar]
61. 61.

    McInnes G, Sharo AG, Koleske ML, Brown JEH, Norstad M et al. 2021. Opportunities and challenges for the computational interpretation of rare variation in clinically important genes. Am. J. Hum. Genet. 108:535–48
    [Google Scholar]
62. 62.

    Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR et al. 2017. Use of exome sequencing for infants in intensive care units: ascertainment of severe single-gene disorders and effect on medical management. JAMA Pediatr 171:e173438
    [Google Scholar]
63. 63.

    Mestek-Boukhibar L, Clement E, Jones WD, Drury S, Ocaka L et al. 2018. Rapid Paediatric Sequencing (RaPS): comprehensive real-life workflow for rapid diagnosis of critically ill children. J. Med. Genet. 55:721–28
    [Google Scholar]
64. 64.

    Miller DE, Sulovari A, Wang T, Loucks H, Hoekzema K et al. 2021. Targeted long-read sequencing identifies missing disease-causing variation. Am. J. Hum. Genet. 108:1436–49
    [Google Scholar]
65. 65.

    Miller DT, Lee K, Chung WK, Gordon AS, Herman GE et al. 2021. ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 23:1381–90
    [Google Scholar]
66. 66.

    Miller DT, Lee K, Gordon AS, Amendola LM, Adelman K et al. 2021. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2021 update: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 23:1391–98
    [Google Scholar]
67. 67.

    Mitani T, Isikay S, Gezdirici A, Gulec EY, Punetha J et al. 2021. High prevalence of multilocus pathogenic variation in neurodevelopmental disorders in the Turkish population. Am. J. Hum. Genet. 108:1981–2005
    [Google Scholar]
68. 68.

    Monaghan KG, Leach NT, Pekarek D, Prasad P, Rose NC et al. 2020. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 22:675–80
    [Google Scholar]
69. 69.

    Natl. Hum. Genome Res. Inst. 2021. DNA sequencing costs: data. National Human Genome Research Institute https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data
    [Google Scholar]
70. 70.

    Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK et al. 2010. Exome sequencing identifies the cause of a Mendelian disorder. Nat. Genet. 42:30–35
    [Google Scholar]
71. 71.

    Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW et al. 2009. Targeted capture and massively parallel sequencing of 12 human exomes. Nature 461:272–76
    [Google Scholar]
72. 72.

    NICUSeq Study Group. 2021. Effect of whole-genome sequencing on the clinical management of acutely ill infants with suspected genetic disease: a randomized clinical trial. JAMA Pediatr 175:1218–26
    [Google Scholar]
73. 73.

    Ouyang X, Zhang Y, Zhang L, Luo J, Zhang T et al. 2021. Clinical utility of rapid exome sequencing combined with mitochondrial DNA sequencing in critically ill pediatric patients with suspected genetic disorders. Front. Genet. 12:725259
    [Google Scholar]
74. 74.

    Owen MJ, Lefebvre S, Hansen C, Kunard CM, David P., Dimmock DP et al. 2022. An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases. Nat. Commun. In press
    [Google Scholar]
75. 75.

    Owen MJ, Niemi AK, Dimmock DP, Speziale M, Nespeca M et al. 2021. Rapid sequencing-based diagnosis of thiamine metabolism dysfunction syndrome. N. Engl. J. Med. 384:2159–61
    [Google Scholar]
76. 76.

    Perrier S, Gauquelin L, Wambach JA, Bernard G. 2021. Distinguishing severe phenotypes associated with pathogenic variants in POLR3A. Am. J. Med. Genet. A 188:708–12
    [Google Scholar]
77. 77.

    Petrikin JE, Cakici JA, Clark MM, Willig LK, Sweeney NM et al. 2018. The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants. NPJ Genom. Med. 3:6
    [Google Scholar]
78. 78.

    Platt R, Simon GE, Hernandez AF. 2021. Is learning worth the trouble?—improving health care system participation in embedded research. N. Engl. J. Med. 385:5–7
    [Google Scholar]
79. 79.

    Powis Z, Farwell Hagman KD, Blanco K, Au M, Graham JM et al. 2020. When moments matter: finding answers with rapid exome sequencing. Mol. Genet. Genom. Med. 8:e1027
    [Google Scholar]
80. 80.

    Ruppel H, Liu V. 2019. To catch a killer: electronic sepsis alert tools reaching a fever pitch?. BMJ Qual. Saf. 28:693–96
    [Google Scholar]
81. 81.

    Sanford EF, Clark MM, Farnaes L, Williams MR, Perry JC et al. 2019. Rapid whole genome sequencing has clinical utility in children in the PICU. Pediatr. Crit. Care Med. 20:1007–20
    [Google Scholar]
82. 82.

    Sanford EF, Jones MC, Brigger M, Hammer M, Giudugli L et al. 2020. Postmortem diagnosis of PPA2-associated sudden cardiac death from dried blood spot in a neonate presenting with vocal cord paralysis. Cold Spring Harb. Mol. Case Stud. 6:a005611
    [Google Scholar]
83. 83.

    Saunders CJ, Miller NA, Soden SE, Dinwiddie DL, Noll A et al. 2012. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units. Sci. Transl. Med. 4:154ra35
    [Google Scholar]
84. 84.

    Scholz T, Blohm ME, Kortum F, Bierhals T, Lessel D et al. 2021. Whole-exome sequencing in critically ill neonates and infants: diagnostic yield and predictability of monogenic diagnosis. Neonatology 118:454–61
    [Google Scholar]
85. 85.

    Shafin K, Pesout T, Lorig-Roach R, Haukness M, Olsen HE et al. 2020. Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes. Nat. Biotechnol. 38:1044–53
    [Google Scholar]
86. 86.

    Smigiel R, Biela M, Szmyd K, Bloch M, Szmida E et al. 2020. Rapid whole-exome sequencing as a diagnostic tool in a neonatal/pediatric intensive care unit. J. Clin. Med. 9:2220
    [Google Scholar]
87. 87.

    Smith HS, Swint JM, Lalani SR, de Oliveira Otto MC, Yamal JM et al. 2020. Exome sequencing compared with standard genetic tests for critically ill infants with suspected genetic conditions. Genet. Med. 22:1303–10
    [Google Scholar]
88. 88.

    Sobesky R, Guillaud O, Bouzbib C, Sogni P, Poujois A et al. 2021. Non-invasive diagnosis and follow-up of rare genetic liver diseases. Clin. Res. Hepatol. Gastroenterol. 46:101768
    [Google Scholar]
89. 89.

    Stark Z, Dolman L, Manolio TA, Ozenberger B, Hill SL et al. 2019. Integrating genomics into healthcare: a global responsibility. Am. J. Hum. Genet. 104:13–20
    [Google Scholar]
90. 90.

    Stark Z, Lunke S, Brett GR, Tan NB, Stapleton R et al. 2018. Meeting the challenges of implementing rapid genomic testing in acute pediatric care. Genet. Med. 20:1554–63
    [Google Scholar]
91. 91.

    Swaggart KA, Swarr DT, Tolusso LK, He H, Dawson DB, Suhrie KR 2019. Making a genetic diagnosis in a level IV neonatal intensive care unit population: Who, when, how, and at what cost?. J. Pediatr. 213:211–17.e4
    [Google Scholar]
92. 92.

    Thakur A, Parvez MM, Leeder JS, Prasad B 2021. Ontogeny of drug-metabolizing enzymes. Methods Mol. Biol. 2342:551–93
    [Google Scholar]
93. 93.

    Thomas RH, Berkovic SF. 2014. The hidden genetics of epilepsy—a clinically important new paradigm. Nat. Rev. Neurol. 10:283–92
    [Google Scholar]
94. 94.

    Tolusso LK, Hazelton P, Wong B, Swarr DT. 2021. Beyond diagnostic yield: prenatal exome sequencing results in maternal, neonatal, and familial clinical management changes. Genet. Med. 23:909–17
    [Google Scholar]
95. 95.

    US Food Drug Adm. 2021. Real-world evidence. US Food and Drug Administration https://www.fda.gov/science-research/science-and-research-special-topics/real-world-evidence
    [Google Scholar]
96. 96.

    Vale AM, Schroeder HW Jr. 2010. Clinical consequences of defects in B-cell development. J. Allergy Clin. Immunol. 125:778–87
    [Google Scholar]
97. 97.

    van Diemen CC, Kerstjens-Frederikse WS, Bergman KA, de Koning TJ, Sikkema-Raddatz B et al. 2017. Rapid targeted genomics in critically ill newborns. Pediatrics 140:e20162854
    [Google Scholar]
98. 98.

    Wang H, Lu Y, Dong X, Lu G, Cheng G et al. 2020. Optimized trio genome sequencing (OTGS) as a first-tier genetic test in critically ill infants: practice in China. Hum. Genet. 139:473–82
    [Google Scholar]
99. 99.

    Wang H, Qian Y, Lu Y, Qin Q, Lu G et al. 2020. Clinical utility of 24-h rapid trio-exome sequencing for critically ill infants. NPJ Genom. Med. 5:20
    [Google Scholar]
100. 100.

     Wapner RJ. 2021. Expanding our understanding of fetal genetic diseases: the beginning of in utero precision medicine. BJOG 128:430
     [Google Scholar]
101. 101.

     Warnat-Herresthal S, Schultze H, Shastry KL, Manamohan S, Mukherjee S et al. 2021. Swarm learning for decentralized and confidential clinical machine learning. Nature 594:265–70
     [Google Scholar]
102. 102.

     Williams JK, Cashion AK, Shekar S, Ginsburg GS. 2016. Genomics, clinical research, and learning health care systems: strategies to improve patient care. Nurs. Outlook 64:225–28
     [Google Scholar]
103. 103.

     Williams MS. 2019. Early lessons from the implementation of genomic medicine programs. Annu. Rev. Genom. Hum. Genet. 20:389–411
     [Google Scholar]
104. 104.

     Willig LK, Petrikin JE, Smith LD, Saunders CJ, Thiffault I et al. 2015. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir. Med. 3:377–87
     [Google Scholar]
105. 105.

     Wojcik MH, Reimers R, Poorvu T, Agrawal PB. 2020. Genetic diagnosis in the fetus. J. Perinatol. 40:997–1006
     [Google Scholar]
106. 106.

     Wojcik MH, Schwartz TS, Thiele KE, Paterson H, Stadelmaier R et al. 2019. Infant mortality: the contribution of genetic disorders. J. Perinatol. 39:1611–19
     [Google Scholar]
107. 107.

     Wojcik MH, Schwartz TS, Yamin I, Edward HL, Genetti CA et al. 2018. Genetic disorders and mortality in infancy and early childhood: delayed diagnoses and missed opportunities. Genet. Med. 20:1396–404
     [Google Scholar]
108. 108.

     Worthey EA, Mayer AN, Syverson GD, Helbling D, Bonacci BB et al. 2011. Making a definitive diagnosis: successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease. Genet. Med. 13:255–62
     [Google Scholar]
109. 109.

     Wouters RHP, van der Graaf R, Rigter T, Bunnik EM, Ploem MC et al. 2021. Towards a responsible transition to learning healthcare systems in precision medicine: ethical points to consider. J. Pers. Med. 11:539
     [Google Scholar]
110. 110.

     Wu B, Kang W, Wang Y, Zhuang D, Chen L et al. 2021. Application of full-spectrum rapid clinical genome sequencing improves diagnostic rate and clinical outcomes in critically ill infants in the China Neonatal Genomes Project. Crit. Care Med. 49:1674–83
     [Google Scholar]
111. 111.

     Wu ET, Hwu WL, Chien YH, Hsu C, Chen TF et al. 2019. Critical trio exome benefits in-time decision-making for pediatric patients with severe illnesses. Pediatr. Crit. Care Med. 20:1021–26
     [Google Scholar]