Clinical Impact and Cost-Effectiveness of Whole Exome Sequencing as a Diagnostic Tool: A Pediatric Center’s Experience

Frontiers in Pediatrics

Volumn 3, Issue , 2015, Pages

  Valencia, C Alexander ^a   Husami, Ammar ^a   Holle, Jennifer ^a   Johnson, Judith A ^a   Qian, Yaping ^b   Mathur, Abhinav ^a   Wei, Chao ^a   Indugula, Subba Rao ^a   Zou, Fanggeng ^a   Meng, Haiying ^a   Wang, Lijun ^a   Li, Xia ^a   Fisher, Rachel ^a   Tan, Tony ^a   Hogart Begtrup, Amber ^a   Collins, Kathleen ^a   Wusik, Katie A ^a   Neilson, Derek ^a   Burrow, Thomas ^a   Schorry, Elizabeth ^a   Hopkin, Robert ^a   Keddache, Mehdi ^a   Harley, John Barker ^a,c   Kaufman, Kenneth M ^a,c   Zhang, Kejian ^a   more..

^a UNIVERSITY OF CINCINNATI COLLEGE OF MEDICINE   (United States)

^b Myriad Genetic Laboratories   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

children; clinical utility; diagnosis; next generation sequencing; pediatrics; whole exome sequencing

Indexed keywords

EID: 84946084988     PISSN: None     EISSN: 22962360     Source Type: Journal    
DOI: 10.3389/fped.2015.00067     Document Type: Article

References (55)

1. McCandless SE Brunger JW Cassidy SB. The burden of genetic disease on inpatient care in a children’s hospital. Am J Hum Genet (2004) 74:121–7.10.1086/38105314681831
2. Gahl WA Markello TC Toro C Fajardo KF Sincan M Gill F et al. The national institutes of health undiagnosed diseases program: insights into rare diseases. Genet Med (2012) 14:51–9.10.1038/gim.0b013e318232a00522237431
3. Ng SB Turner EH Robertson PD Flygare SD Bigham AW Lee C et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature (2009) 461:272–6.10.1038/nature0825019684571
4. Lupski JR Reid JG Gonzaga-Jauregui C Rio Deiros D Chen DCY Nazareth L et al. Whole-genome sequencing in a patient with Charcot-Marie-Tooth neuropathy. N Engl J Med (2010) 362:1181–91.10.1056/NEJMoa090809420220177
5. Vissers LELM de Ligt J Gilissen C Janssen I Steehouwer M de Vries P et al. A de novo paradigm for mental retardation. Nat Genet (2010) 42:1109–12.10.1038/ng.71221076407
6. Bainbridge MN Wiszniewski W Murdock DR Friedman J Gonzaga-Jauregui C Newsham I et al. Whole-genome sequencing for optimized patient management. Sci Transl Med (2011) 3:87re3.10.1126/scitranslmed.300224321677200
7. Gonzaga-Jauregui C Lupski JR Gibbs RA. Human genome sequencing in health and disease. Annu Rev Med (2012) 63:35–61.10.1146/annurev-med-051010-16264422248320
8. De Ligt J Willemsen MH van Bon BWM Kleefstra T Yntema HG Kroes T et al. Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med (2012) 367:1921–9.10.1056/NEJMoa120652423033978
9. Rauch A Wieczorek D Graf E Wieland T Endele S Schwarzmayr T et al. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet (2012) 380:1674–82.10.1016/S0140-6736(12)61480-923020937
10. Hoischen A van Bon BWM Gilissen C Arts P van Lier B Steehouwer M et al. De novo mutations of SETBP1 cause Schinzel-Giedion syndrome. Nat Genet (2010) 42:483–5.10.1038/ng.58120436468
11. Johnson JO Mandrioli J Benatar M Abramzon Y Van Deerlin VM Trojanowski JQ et al. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron (2010) 68:857–64.10.1016/j.neuron.2010.11.03621145000
12. Krawitz PM Schweiger MR Rödelsperger C Marcelis C Kölsch U Meisel C et al. Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome. Nat Genet (2010) 42:827–9.10.1038/ng.65320802478
13. Lalonde E Albrecht S Ha KCH Jacob K Bolduc N Polychronakos C et al. Unexpected allelic heterogeneity and spectrum of mutations in Fowler syndrome revealed by next-generation exome sequencing. Hum Mutat (2010) 31:918–23.10.1002/humu.2129320518025
14. Musunuru K Pirruccello JP Do R Peloso GM Guiducci C Sougnez C et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med (2010) 363:2220–7.10.1056/NEJMoa100292620942659
15. Ng SB Bigham AW Buckingham KJ Hannibal MC McMillin MJ Gildersleeve HI et al. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet (2010) 42:790–3.10.1038/ng.64620711175
16. Ng SB Buckingham KJ Lee C Bigham AW Tabor HK Dent KM et al. Exome sequencing identifies the cause of a mendelian disorder. Nat Genet (2010) 42:30–5.10.1038/ng.49919915526
17. Pierce SB Walsh T Chisholm KM Lee MK Thornton AM Fiumara A et al. Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault syndrome. Am J Hum Genet (2010) 87:282–8.10.1016/j.ajhg.2010.07.00720673864
18. Iglesias A Anyane-Yeboa K Wynn J Wilson A Truitt Cho M Guzman E et al. The usefulness of whole-exome sequencing in routine clinical practice. Genet Med (2014) 16(12):922–31.10.1038/gim.2014.5824901346
19. Yang Y Muzny DM Reid JG Bainbridge MN Willis A Ward PA et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med (2013) 369:1502–11.10.1056/NEJMoa130655524088041
20. Yang Y Muzny DM Xia F Niu Z Person R Ding Y et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA (2014) 312(18):1870–9.10.1001/jama.2014.1460125326635
21. Lee H Deignan JL Dorrani N Strom SP Kantarci S Quintero-Rivera F et al. Clinical exome sequencing for genetic identification of rare mendelian disorders. JAMA (2014) 312:1880–7.10.1001/jama.2014.1460425326637
22. Ellard S Kivuva E Turnpenny P Stals K Johnson M Xie W et al. An exome sequencing strategy to diagnose lethal autosomal recessive disorders. Eur J Hum Genet (2015) 23:401–4.10.1038/ejhg.2014.12024961629
23. Patel ZH Kottyan LC Lazaro S Williams MS Ledbetter DH Tromp H et al. The struggle to find reliable results in exome sequencing data: filtering out mendelian errors. Front Genet (2014) 5:16.10.3389/fgene.2014.0001624575121
24. Richards CS Bale S Bellissimo DB Das S Grody WW Hegde MR et al. Molecular subcommittee of the ACMG laboratory quality assurance committee. ACMG recommendations for standards for interpretation and reporting of sequence variations: revisions 2007. Genet Med (2008) 10:294–300.10.1097/GIM.0b013e31816b5cae18414213
25. Green RC Berg JS Grody WW Kalia SS Korf BR Martin CL et al. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med (2013) 15:565–74.10.1038/gim.2013.7323788249
26. Lindsley AW Qian Y Valencia CA Shah K Zhang K Assa’ad A. Combined immune deficiency in a patient with a novel NFKB2 mutation. J Clin Immunol (2014) 34:910–5.10.1007/s10875-014-0095-325205549
27. Sun X Marks DL Park WD Wheatley CL Puri V O’Brien JF et al. Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1. Am J Hum Genet (2001) 68:1361–72.10.1086/32059911349231
28. Greer WL Dobson MJ Girouard GS Byers DM Riddell DC Neumann PE. Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain. Am J Hum Genet (1999) 65:1252–60.10.1086/30262010521290
29. Marlin S Garabédian EN Roger G Moatti L Matha N Lewin P et al. Connexin 26 gene mutations in congenitally deaf children: pitfalls for genetic counseling. Arch Otolaryngol Head Neck Surg (2001) 127:927–33.10.1001/archotol.127.8.92711493200
30. Giunta C Nuytinck L Raghunath M Hausser I De Paepe A Steinmann B. Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome. Am J Med Genet (2002) 109:284–90.10.1002/ajmg.1037311992482
31. Martin E Palmic N Sanquer S Lenoir C Hauck F Mongellaz C et al. CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature (2014) 510:288–92.10.1038/nature1338624870241
32. Andersen PS Havndrup O Bundgaard H Moolman-Smook JC Larsen LA Mogensen J et al. Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations. J Med Genet (2001) 38:E43.10.1136/jmg.38.12.e43
33. Ogawa N Imai Y Takahashi Y Nawata K Hara K Nishimura H et al. Evaluating Japanese patients with the Marfan syndrome using high-throughput microarray-based mutational analysis of fibrillin-1 gene. Am J Cardiol (2011) 108:1801–7.10.1016/j.amjcard.2011.07.05321907952
34. Ohno K Wang HL Milone M Bren N Brengman JM Nakano S et al. Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit. Neuron (1996) 17:157–70.10.1016/S0896-6273(00)80289-58755487
35. Saitsu H Kato M Okada I Orii KE Higuchi T Hoshino H et al. STXBP1 mutations in early infantile epileptic encephalopathy with suppression-burst pattern. Epilepsia (2010) 51:2397–405.10.1111/j.1528-1167.2010.02728.x20887364
36. Tavtigian SV Simard J Rommens J Couch F Shattuck-Eidens D Neuhausen S et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet (1996) 12:333–7.10.1038/ng0396-3338589730
37. Støy J Edghill EL Flanagan SE Ye H Paz VP Pluzhnikov A et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A (2007) 104:15040–4.10.1073/pnas.070729110417855560
38. Dabby R Sadeh M Gilad R Lampl Y Cohen S Inbar S et al. Chronic non-paroxysmal neuropathic pain – novel phenotype of mutation in the sodium channel SCN9A gene. J Neurol Sci (2011) 301:90–2.10.1016/j.jns.2010.10.00621094958
39. Faber CG Hoeijmakers JGJ Ahn H-S Cheng X Han C Choi J-S et al. Gain of function Naν1.7 mutations in idiopathic small fiber neuropathy. Ann Neurol (2012) 71:26–39.10.1002/ana.2248521698661
40. Yuan R Zhang X Deng Q Si D Wu Y Gao F et al. Two novel SCN9A gene heterozygous mutations may cause partial deletion of pain perception. Pain Med (2011) 12:1510–4.10.1111/j.1526-4637.2011.01237.x21939494
41. Kostareva A Sjoberg G Gudkova A Smolina N Semernin E Shlyakhto E et al. Desmin A213V substitution represents a rare polymorphism but not a mutation and is more prevalent in patients with heart dilation of various origins. Acta Myol (2011) 30(1):42–5.21842594
42. Millar S Carson D. Clinical phenotypes of autoimmune polyendocrinopathycandidiasis-ectodermal dystrophy seen in the Northern Ireland paediatric population over the last 30 years. Ulster Med J (2012) 81(3):118–22.23620608
43. Kytövuori L Seppänen A Martikainen MH Moilanen JS Kamppari S Särkioja T et al. WFS1 variants in finnish patients with diabetes mellitus, sensorineural hearing impairment or optic atrophy, and in suicide victims. J Hum Genet (2013) 58:495–500.10.1038/jhg.2013.2923595122
44. Singh NA Pappas C Dahle EJ Claes LRF Pruess TH De Jonghe P et al. A role of SCN9A in human epilepsies, as a cause of febrile seizures and as a potential modifier of Dravet syndrome. PLoS Genet (2009) 5:e1000649.10.1371/journal.pgen.100064919763161
45. Willig LK Petrikin JE Smith LD Saunders CJ Thiffault I Miller NA et al. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: a retrospective analysis of diagnostic and clinical findings. Lancet Respir Med (2015) 3(5):377–87.10.1016/S2213-2600(15)00139-325937001
46. Shevell M Ashwal S Donley D Flint J Gingold M Hirtz D et al. Practice parameter: evaluation of the child with global developmental delay: report of the quality standards subcommittee of the American academy of neurology and the practice committee of the child neurology society. Neurology (2003) 60:367–80.10.1212/01.WNL.0000031431.81555.1612578916
47. Shaffer LG American College of Medical Genetics Professional Practice and Guidelines Committee. American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genet Med (2005) 7(9):650–4.10.1097/01.gim.0000186545.83160.1e16301868
48. Miller DT Adam MP Aradhya S Biesecker LG Brothman AR Carter NP et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet (2010) 86:749–64.10.1016/j.ajhg.2010.04.00620466091
49. Valencia CA Ankala A Rhodenizer D Bhide S Littlejohn MR Keong LM et al. Comprehensive mutation analysis for congenital muscular dystrophy: a clinical PCR-based enrichment and next-generation sequencing panel. PLoS One (2013) 8:e53083.10.1371/journal.pone.005308323326386
50. Nijman IJ van Montfrans JM Hoogstraat M Boes ML van de Corput L Renner ED et al. Targeted next-generation sequencing: a novel diagnostic tool for primary immunodeficiencies. J Allergy Clin Immunol (2014) 133:529–34.10.1016/j.jaci.2013.08.03224139496
51. Chen K Coonrod EM Kumánovics A Franks ZF Durtschi JD Margraf RL et al. Germline mutations in NFKB2 implicate the noncanonical NF-κB pathway in the pathogenesis of common variable immunodeficiency. Am J Hum Genet (2013) 93:812–24.10.1016/j.ajhg.2013.09.00924140114
52. Liu Y Hanson S Gurugama P Jones A Clark B Ibrahim MAA. Novel NFKB2 mutation in early-onset CVID. J Clin Immunol (2014) 34:686–90.10.1007/s10875-014-0064-x24888602
53. Pohl E Aykut A Beleggia F Karaca E Durmaz B Keupp K et al. A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome. Hum Genet (2013) 132:1311–20.10.1007/s00439-013-1337-923851939
54. Bainbridge MN Hu H Muzny DM Musante L Lupski JR Graham BH et al. De novo truncating mutations in ASXL3 are associated with a novel clinical phenotype with similarities to Bohring-Opitz syndrome. Genome Med (2013) 5:11.10.1186/gm41523383720
55. Lupski JR Gonzaga-Jauregui C Yang Y Bainbridge MN Jhangiani S Buhay CJ et al. Exome sequencing resolves apparent incidental findings and reveals further complexity of SH3TC2 variant alleles causing Charcot-Marie-Tooth neuropathy. Genome Med (2013) 5:57.10.1186/gm46123806086