Exome/Genome Sequencing in Undiagnosed Syndromes.
Mendelian diseases
exome sequencing
genome sequencing
next-generation sequencing
rare/ultrarare diseases
undiagnosed diseases
Journal
Annual review of medicine
ISSN: 1545-326X
Titre abrégé: Annu Rev Med
Pays: United States
ID NLM: 2985151R
Informations de publication
Date de publication:
27 01 2023
27 01 2023
Historique:
entrez:
27
1
2023
pubmed:
28
1
2023
medline:
1
2
2023
Statut:
ppublish
Résumé
Exome sequencing (ES) and genome sequencing (GS) have radically transformed the diagnostic approach to undiagnosed rare/ultrarare Mendelian diseases. Next-generation sequencing (NGS), the technology integral for ES, GS, and most large (100+) gene panels, has enabled previously unimaginable diagnoses, changes in medical management, new treatments, and accurate reproductive risk assessments for patients, as well as new disease gene discoveries. Yet, challenges remain, as most individuals remain undiagnosed with current NGS. Improved NGS technology has resulted in long-read sequencing, which may resolve diagnoses in some patients who do not obtain a diagnosis with current short-read ES and GS, but its effectiveness is unclear, and it is expensive. Other challenges that persist include the resolution of variants of uncertain significance, the urgent need for patients with ultrarare disorders to have access to therapeutics, the need for equity in patient access to NGS-based testing, and the study of ethical concerns. However, the outlook for undiagnosed disease resolution is bright, due to continual advancements in the field.
Identifiants
pubmed: 36706750
doi: 10.1146/annurev-med-042921-110721
pmc: PMC10483513
mid: NIHMS1926912
doi:
Types de publication
Journal Article
Review
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
489-502Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG007672
Pays : United States
Références
Sci Transl Med. 2014 Dec 3;6(265):265ra168
pubmed: 25473036
JMIR Pediatr Parent. 2022 Jan 6;5(1):e31411
pubmed: 34989690
J Med Genet. 2012 Jun;49(6):353-61
pubmed: 22581936
Nat Genet. 2007 Jul;39(7 Suppl):S43-7
pubmed: 17597781
N Engl J Med. 2019 Jun 20;380(25):2478-2480
pubmed: 31216405
Genet Med. 2013 Jul;15(7):565-74
pubmed: 23788249
Am J Hum Genet. 2019 Sep 5;105(3):448-455
pubmed: 31491408
Genet Med. 2017 Feb;19(2):209-214
pubmed: 27441994
Nat Genet. 2010 Dec;42(12):1109-12
pubmed: 21076407
Orphanet J Rare Dis. 2017 Apr 17;12(1):71
pubmed: 28416019
Am J Med Genet A. 2020 Aug;182(8):1947-1951
pubmed: 32445275
J Genet Couns. 2018 Aug;27(4):935-946
pubmed: 29297108
J Med Genet. 2015 May;52(5):330-7
pubmed: 25725044
Genet Med. 2018 Jan;20(1):159-163
pubmed: 28640241
Science. 2022 Apr;376(6588):44-53
pubmed: 35357919
Am J Med Genet A. 2020 May;182(5):1053-1065
pubmed: 32083401
Genet Med. 2020 Jul;22(7):1269-1275
pubmed: 32366967
Ann Neurol. 2015 Dec;78(6):995-9
pubmed: 26369628
Annu Rev Genomics Hum Genet. 2020 Aug 31;21:305-326
pubmed: 32339034
Health Policy. 2022 Apr;126(4):337-345
pubmed: 35317923
Cold Spring Harb Perspect Med. 2015 Oct 05;5(12):
pubmed: 26438605
Genet Med. 2019 Apr;21(4):798-812
pubmed: 30655598
N Engl J Med. 2015 Jun 4;372(23):2235-42
pubmed: 26014595
Eur J Hum Genet. 2022 Apr;30(4):428-438
pubmed: 34974531
JAMA. 2014 Nov 12;312(18):1870-9
pubmed: 25326635
NPJ Genom Med. 2016 Jan 13;1:
pubmed: 28567303
N Engl J Med. 2019 Oct 24;381(17):1644-1652
pubmed: 31597037
Am J Hum Genet. 2015 Aug 6;97(2):199-215
pubmed: 26166479
Hum Genet. 2021 Oct;140(10):1403-1416
pubmed: 34368901
Genet Med. 2022 Jun;24(6):1336-1348
pubmed: 35305867
Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000265
pubmed: 27148562
Nat Rev Genet. 2011 Sep 27;12(11):745-55
pubmed: 21946919
Genet Med. 2015 Oct;17(10):774-81
pubmed: 25590979
NPJ Genom Med. 2018 Apr 4;3:10
pubmed: 29644095
Hum Mutat. 2019 Aug;40(8):1115-1126
pubmed: 31264822
Genet Med. 2022 Jan;24(1):109-118
pubmed: 34906478
Genet Med. 2016 Jul;18(7):696-704
pubmed: 26633542
Genet Med. 2019 Jun;21(6):1267-1270
pubmed: 31015575
Nature. 2014 Jul 17;511(7509):344-7
pubmed: 24896178
Genet Med. 2017 Sep;19(9):1040-1048
pubmed: 28252636
Lancet Respir Med. 2015 May;3(5):377-87
pubmed: 25937001
Sci Transl Med. 2012 Oct 3;4(154):154ra135
pubmed: 23035047
Genet Med. 2018 Oct;20(10):1122-1130
pubmed: 29446766
Genet Med. 2014 Oct;16(10):736-7
pubmed: 24651604
Genet Med. 2021 Feb;23(2):259-271
pubmed: 33093671
Mayo Clin Proc. 2001 Aug;76(8):777-83
pubmed: 11499815
Annu Rev Med. 2022 Jan 27;73:575-585
pubmed: 35084988
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Cold Spring Harb Mol Case Stud. 2015 Oct;1(1):a000257
pubmed: 27148561
JAMA. 2014 Nov 12;312(18):1880-7
pubmed: 25326637
Genet Med. 2019 Jan;21(1):173-180
pubmed: 29765138
Eur J Hum Genet. 2017 Dec;25(12):1303-1312
pubmed: 29158552
N Engl J Med. 2018 Nov 29;379(22):2131-2139
pubmed: 30304647
Nat Biotechnol. 2016 Aug 9;34(8):810-1
pubmed: 27504770
Am J Med Genet. 1985 Jun;21(2):231-42
pubmed: 4014310
Genet Med. 2012 Jan;14(1):51-9
pubmed: 22237431
Genet Med. 2019 Apr;21(4):861-866
pubmed: 30214068
JAMA Pediatr. 2017 Sep 1;171(9):855-862
pubmed: 28759686
Genet Med. 2017 Sep;19(9):1055-1063
pubmed: 28333917
Med J Aust. 2018 Aug 3;209(5):197-199
pubmed: 29621958
Genet Med. 2021 Nov;23(11):2029-2037
pubmed: 34211152
Science. 2001 Feb 16;291(5507):1304-51
pubmed: 11181995
Clin Genet. 2016 Mar;89(3):275-84
pubmed: 26283276
PLoS Genet. 2022 Jun 2;18(6):e1010228
pubmed: 35653343
Front Genet. 2021 Jun 17;12:674295
pubmed: 34220947
Genet Med. 2014 Feb;16(2):176-82
pubmed: 23928913
Am J Hum Genet. 2019 Jan 3;104(1):13-20
pubmed: 30609404
J Genet Couns. 2016 Oct;25(5):1019-31
pubmed: 26868367
BMC Genomics. 2012 Jul 24;13:341
pubmed: 22827831
Hum Mutat. 2015 Oct;36(10):928-30
pubmed: 26220891
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Genet Med. 2014 Dec;16(12):922-31
pubmed: 24901346
Child Care Health Dev. 2007 May;33(3):296-307
pubmed: 17439444
Am J Hum Genet. 2018 Aug 2;103(2):245-260
pubmed: 30057031
J Med Genet. 2017 Mar;54(3):155-156
pubmed: 27899421
Trends Genet. 2018 Sep;34(9):666-681
pubmed: 29941292
Nat Genet. 2010 Jan;42(1):30-5
pubmed: 19915526
N Engl J Med. 2018 Oct 04;379(14):1353-1362
pubmed: 30281996
Ann Lab Med. 2019 Sep;39(5):421-429
pubmed: 31037860
Eur J Med Genet. 2019 Jun;62(6):103529
pubmed: 30165243
Am J Med Genet A. 2022 Apr;188(4):1088-1101
pubmed: 34981646
BMC Med Genomics. 2016 Aug 11;9(1):52
pubmed: 27514372
J Appl Genet. 2011 Nov;52(4):413-35
pubmed: 21698376
N Engl J Med. 2013 Oct 17;369(16):1502-11
pubmed: 24088041
Genet Med. 2019 Jan;21(1):161-172
pubmed: 29907797
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5473-8
pubmed: 25827230
Am J Med Genet. 2001 Oct 1;103(2):106-14
pubmed: 11568915
Lancet. 2012 Nov 10;380(9854):1674-82
pubmed: 23020937
Bioorg Med Chem Lett. 2017 Jul 1;27(13):2962-2966
pubmed: 28512024
Expert Rev Mol Diagn. 2011 Nov;11(8):855-68
pubmed: 22022947
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669
Clin Genet. 2016 Feb;89(2):173-81
pubmed: 25678066
Genet Med. 2013 Sep;15(9):748-9
pubmed: 23970068
Genet Med. 2022 Jul;24(7):1407-1414
pubmed: 35802134