A Clinician’s perspective on clinical exome sequencing

Human Genetics

Volumn 135, Issue 6, 2016, Pages 643-654

  O’Donnell Luria, Anne H ^a,b,d   Miller, David T ^a,c,d  

^a BOSTON CHILDREN S HOSPITAL   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c Claritas Genomics   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA SEQUENCE; EXOME; GENETIC SCREENING; GENETICS; HUMAN; MOLECULAR PATHOLOGY; PHYSICIAN; TRENDS;

EXOME; GENETIC TESTING; HUMANS; PATHOLOGY, MOLECULAR; PHYSICIANS; SEQUENCE ANALYSIS, DNA;

EID: 84964497588     PISSN: 03406717     EISSN: 14321203     Source Type: Journal    
DOI: 10.1007/s00439-016-1662-x     Document Type: Review

References (58)

1. ACMG Board of Directors (2012) Points to consider in the clinical application of genomic sequencing. Genet Med Off J Am Coll Med Genet 14:759–761. doi:10.1038/gim.2012.74
2. ACMG Board of Directors (2013) Points to consider for informed consent for genome/exome sequencing. Genet Med Off J Am Coll Med Genet 15:748–749. doi:10.1038/gim.2013.94
3. Alamillo CL, Powis Z, Farwell K et al (2015) Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies. Prenat Diagn 35:1073–1078. doi:10.1002/pd.4648
4. ®), an online catalog of human genes and genetic disorders. Nucl Acids Res 43:D789–D798. doi:10.1093/nar/gku1205
5. Amendola LM, Dorschner MO, Robertson PD et al (2015) Actionable exomic incidental findings in 6503 participants: challenges of variant classification. Genome Res 25:305–315. doi:10.1101/gr.183483.114
6. Amor D, Rose C, White S, et al (2016) POSSUMweb. http://www.possum.net.au. Accessed 25 Jan 2016
7. Bell CJ, Dinwiddie DL, Miller NA et al (2011) Carrier testing for severe childhood recessive diseases by next-generation sequencing. Sci Transl Med 3:65ra4. doi:10.1126/scitranslmed.3001756
8. Bernhardt BA, Roche MI, Perry DL et al (2015) Experiences with obtaining informed consent for genomic sequencing. Am J Med Genet A 167A:2635–2646. doi:10.1002/ajmg.a.37256
9. Buske OJ, Girdea M, Dumitriu S et al (2015) PhenomeCentral: a portal for phenotypic and genotypic matchmaking of patients with rare genetic diseases. Hum Mutat 36:931–940. doi:10.1002/humu.22851
10. Carss KJ, Hillman SC, Parthiban V et al (2014) Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound. Hum Mol Genet 23:3269–3277. doi:10.1093/hmg/ddu038
11. Chong JX, Buckingham KJ, Jhangiani SN et al (2015) The genetic basis of mendelian phenotypes: discoveries, challenges, and opportunities. Am J Hum Genet 97:199–215. doi:10.1016/j.ajhg.2015.06.009
12. de Ligt J, Willemsen MH, van Bon BWM et al (2012) Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med 367:1921–1929. doi:10.1056/NEJMoa1206524
13. Dorschner MO, Amendola LM, Turner EH et al (2013) Actionable, pathogenic incidental findings in 1,000 participants’ exomes. Am J Hum Genet 93:631–640. doi:10.1016/j.ajhg.2013.08.006
14. Drury S, Williams H, Trump N et al (2015) Exome sequencing for prenatal diagnosis of fetuses with sonographic abnormalities. Prenat Diagn 35:1010–1017. doi:10.1002/pd.4675
15. Farwell KD, Shahmirzadi L, El-Khechen D et al (2015) Enhanced utility of family-centered diagnostic exome sequencing with inheritance model-based analysis: results from 500 unselected families with undiagnosed genetic conditions. Genet Med Off J Am Coll Med Genet 17:578–586. doi:10.1038/gim.2014.154
16. Fernandez BA, Green JS, Bursey F et al (2012) Adult siblings with homozygous G6PC3 mutations expand our understanding of the severe congenital neutropenia type 4 (SCN4) phenotype. BMC Med Genet 13:111. doi:10.1186/1471-2350-13-111
17. Fogel BL, Lee H, Deignan JL et al (2014) Exome sequencing in the clinical diagnosis of sporadic or familial cerebellar ataxia. JAMA Neurol 71:1237–1246. doi:10.1001/jamaneurol.2014.1944
18. Fokkema IFAC, Taschner PEM, Schaafsma GCP et al (2011) LOVD v. 2.0: the next generation in gene variant databases. Hum Mutat 32:557–563. doi:10.1002/humu.21438
19. Fryns J-P, de Ravel TJL (2002) London Dysmorphology Database, London Neurogenetics Database and Dysmorphology Photo Library on CD-ROM [Version 3] 2001R. M. Winter, M. Baraitser, Oxford University Press, ISBN 019851-780, pound sterling 1595. Hum Genet 111:113. doi:10.1007/s00439-002-0759-6
20. Genetic and Rare Diseases (GARD) Information Center: Natl. Inst. Health Off. Rare Dis. https://rarediseases.info.nih.gov/. Accessed 30 Dec 2015
21. Gilissen C, Hehir-Kwa JY, Thung DT et al (2014) Genome sequencing identifies major causes of severe intellectual disability. Nature 511:344–347. doi:10.1038/nature13394
22. Goodwin G, Hawley PP, Miller DT (2016) A case of HDR syndrome and Ichthyosis: dual diagnosis by whole genome sequencing of novel mutations in GATA3 and STS genes. J Clin Endocrinol Metab 101:837–840. doi:10.1210/jc.2015-3704
23. Graungaard AH, Skov L (2007) Why do we need a diagnosis? A qualitative study of parents’ experiences, coping and needs, when the newborn child is severely disabled. Child Care Health Dev 33:296–307. doi:10.1111/j.1365-2214.2006.00666.x
24. Green RC, Berg JS, Grody WW et al (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med Off J Am Coll Med Genet 15:565–574. doi:10.1038/gim.2013.73
25. Green RC, Lautenbach D, McGuire AL (2015) GINA, genetic discrimination, and genomic medicine. N Engl J Med 372:397–399. doi:10.1056/NEJMp1404776
26. Gripp KW, Slavotinek AM, Hall JG, Allanson JE (2013) Handbook of physical measurements, 3rd edn. Oxford University Press, Oxford, UK
27. Groza T, Köhler S, Moldenhauer D et al (2015) The Human phenotype ontology: semantic unification of common and rare disease. Am J Hum Genet 97:111–124. doi:10.1016/j.ajhg.2015.05.020
28. Iglesias A, Anyane-Yeboa K, Wynn J et al (2014) The usefulness of whole-exome sequencing in routine clinical practice. Genet Med Off J Am Coll Med Genet 16:922–931. doi:10.1038/gim.2014.58
29. Jurgens J, Ling H, Hetrick K et al (2015) Assessment of incidental findings in 232 whole-exome sequences from the Baylor-Hopkins Center for Mendelian Genomics. Genet Med Off J Am Coll Med Genet 17:782–788. doi:10.1038/gim.2014.196
30. Landrum MJ, Lee JM, Riley GR et al (2014) ClinVar: public archive of relationships among sequence variation and human phenotype. Nucl Acids Res 42:D980–D985. doi:10.1093/nar/gkt1113
31. Lawrence L, Sincan M, Markello T et al (2014) The implications of familial incidental findings from exome sequencing: the NIH Undiagnosed Diseases Program experience. Genet Med Off J Am Coll Med Genet 16:741–750. doi:10.1038/gim.2014.29
32. Lee H, Deignan JL, Dorrani N et al (2014) Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 312:1880–1887. doi:10.1001/jama.2014.14604
33. Lek M, Karczewski K, Minikel E et al (2015) Analysis of protein-coding genetic variation in 60,706 humans. bioRxiv, Art id 030338
34. Li Y, Salfelder A, Schwab KO et al (2016) Against all odds: blended phenotypes of three single-gene defects. Eur J Hum Genet EJHG. doi:10.1038/ejhg.2015.285
35. McCandless SE, Brunger JW, Cassidy SB (2004) The burden of genetic disease on inpatient care in a children’s hospital. Am J Hum Genet 74:121–127. doi:10.1086/381053
36. Miller DT, Adam MP, Aradhya S et al (2010) Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 86:749–764. doi:10.1016/j.ajhg.2010.04.006
37. ® [Internet]. University of Washington, Seattle. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1116/
38. Philippakis AA, Azzariti DR, Beltran S et al (2015) The Matchmaker exchange: a platform for rare disease gene discovery. Hum Mutat 36:915–921. doi:10.1002/humu.22858
39. Pisano T, Numis AL, Heavin SB et al (2015) Early and effective treatment of KCNQ2 encephalopathy. Epilepsia 56:685–691. doi:10.1111/epi.12984
40. Piton A, Redin C, Mandel J-L (2013) XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet 93:368–383. doi:10.1016/j.ajhg.2013.06.013
41. Posey JE, Rosenfeld JA, James RA et al (2015) Molecular diagnostic experience of whole-exome sequencing in adult patients. Genet Med Off J Am Coll Med Genet. doi:10.1038/gim.2015.142
42. Powis Z, Farwell KD, Alamillo CL, Tang S (2015) Diagnostic exome sequencing for patients with a family history of consanguinity: over 38 % of positive results are not autosomal recessive pattern. J Hum Genet. doi:10.1038/jhg.2015.125
43. Retterer K, Juusola J, Cho MT et al (2015) Clinical application of whole-exome sequencing across clinical indications. Genet Med Off J Am Coll Med Genet. doi:10.1038/gim.2015.148
44. Richards S, Aziz N, Bale S et al (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med Off J Am Coll Med Genet 17:405–424. doi:10.1038/gim.2015.30
45. Shashi V, McConkie-Rosell A, Rosell B et al (2014) The utility of the traditional medical genetics diagnostic evaluation in the context of next-generation sequencing for undiagnosed genetic disorders. Genet Med Off J Am Coll Med Genet 16:176–182. doi:10.1038/gim.2013.99
46. Shashi V, McConkie-Rosell A, Schoch K et al (2015) Practical considerations in the clinical application of whole-exome sequencing. Clin Genet. doi:10.1111/cge.12569
47. Sobreira N, Schiettecatte F, Valle D, Hamosh A (2015) GeneMatcher: a matching tool for connecting investigators with an interest in the same gene. Hum Mutat 36:928–930. doi:10.1002/humu.22844
48. Soden SE, Saunders CJ, Willig LK et al (2014) Effectiveness of exome and genome sequencing guided by acuity of illness for diagnosis of neurodevelopmental disorders. Sci Transl Med 6:265ra168. doi:10.1126/scitranslmed.3010076
49. Stenson PD, Mort M, Ball EV et al (2014) The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Hum Genet 133:1–9. doi:10.1007/s00439-013-1358-4
50. Tammimies K, Marshall CR, Walker S et al (2015) Molecular diagnostic yield of chromosomal microarray analysis and whole-exome sequencing in children with autism spectrum disorder. JAMA 314:895–903. doi:10.1001/jama.2015.10078
51. Taylor JC, Martin HC, Lise S et al (2015) Factors influencing success of clinical genome sequencing across a broad spectrum of disorders. Nat Genet 47:717–726. doi:10.1038/ng.3304
52. The 1000 Genomes Project Consortium (2015) A global reference for human genetic variation. Nature 526:68–74. doi:10.1038/nature15393
53. Valencia CA, Husami A, Holle J et al (2015) Clinical impact and cost-effectiveness of whole exome sequencing as a diagnostic tool: a pediatric center’s experience. Front Pediatr 3:67. doi:10.3389/fped.2015.00067
54. Wallis M, Tsurusaki Y, Burgess T et al (2015) Dual genetic diagnoses: atypical hand-foot-genital syndrome and developmental delay due to de novo mutations in HOXA13 and NRXN1. Am J Med Genet A. doi:10.1002/ajmg.a.37478
55. Wright CF, Fitzgerald TW, Jones WD et al (2015) Genetic diagnosis of developmental disorders in the DDD study: a scalable analysis of genome-wide research data. Lancet Lond Engl 385:1305–1314. doi:10.1016/S0140-6736(14)61705-0
56. Yang Y, Muzny DM, Xia F et al (2014) Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312:1870–1879. doi:10.1001/jama.2014.14601
57. Yavarna T, Al-Dewik N, Al-Mureikhi M et al (2015) High diagnostic yield of clinical exome sequencing in Middle Eastern patients with Mendelian disorders. Hum Genet 134:967–980. doi:10.1007/s00439-015-1575-0
58. Zhu X, Petrovski S, Xie P et al (2015) Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. Genet Med Off J Am Coll Med Genet 17:774–781. doi:10.1038/gim.2014.191