Next-Generation Sequencing in the Field of Primary Immunodeficiencies: Current Yield, Challenges, and Future Perspectives.
Diagnostic yield
Next-generation sequencing
Precision medicine
Primary immunodeficiencies
Whole exome sequencing
Journal
Clinical reviews in allergy & immunology
ISSN: 1559-0267
Titre abrégé: Clin Rev Allergy Immunol
Pays: United States
ID NLM: 9504368
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
accepted:
07
01
2021
pubmed:
6
3
2021
medline:
17
12
2021
entrez:
5
3
2021
Statut:
ppublish
Résumé
Primary immunodeficiencies comprise a group of inborn errors of immunity that display significant clinical and genetic heterogeneity. Next-generation sequencing techniques and predominantly whole exome sequencing have revolutionized the understanding of the genetic and molecular basis of genetic diseases, thereby also leading to a sharp increase in the discovery of new genes associated with primary immunodeficiencies. In this review, we discuss the current diagnostic yield of this generic diagnostic approach by evaluating the studies that have employed next-generation sequencing techniques in cohorts of patients with primary immunodeficiencies. The average diagnostic yield for primary immunodeficiencies is determined to be 29% (range 10-79%) and 38% specifically for whole-exome sequencing (range 15-70%). The significant variation between studies is mainly the result of differences in clinical characteristics of the studied cohorts but is also influenced by varying sequencing approaches and (in silico) gene panel selection. We further discuss other factors contributing to the relatively low yield, including the inherent limitations of whole-exome sequencing, challenges in the interpretation of novel candidate genetic variants, and promises of exploring the non-coding part of the genome. We propose strategies to improve the diagnostic yield leading the way towards expanded personalized treatment in PIDs.
Identifiants
pubmed: 33666867
doi: 10.1007/s12016-021-08838-5
pii: 10.1007/s12016-021-08838-5
pmc: PMC7934351
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
212-225Informations de copyright
© 2021. The Author(s).
Références
J Clin Immunol. 2020 Jan;40(1):24-64
pubmed: 31953710
Front Immunol. 2016 Jun 13;7:220
pubmed: 27379089
Eur J Hum Genet. 2012 May;20(5):490-7
pubmed: 22258526
Genome Res. 2014 Feb;24(2):340-8
pubmed: 24162188
Clin Immunol. 2020 Mar;212:108248
pubmed: 31382036
Clin Genet. 2018 Mar;93(3):647-655
pubmed: 29077208
Hum Hered. 2014;77(1-4):63-72
pubmed: 25060270
J Clin Immunol. 2013 Jan;33(1):1-7
pubmed: 22847546
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):5473-8
pubmed: 25827230
Nature. 2020 Jul;583(7814):90-95
pubmed: 32499645
Nucleic Acids Res. 2017 Feb 28;45(4):1633-1648
pubmed: 27980096
Clin Immunol. 2020 May;214:108376
pubmed: 32135276
J Allergy Clin Immunol. 2016 Oct;138(4):1142-1151.e2
pubmed: 27484032
Front Genet. 2019 May 07;10:426
pubmed: 31134132
J Hum Genet. 2014 Jan;59(1):5-15
pubmed: 24196381
Genet Med. 2018 Oct;20(10):1216-1223
pubmed: 29323667
Nucleic Acids Res. 2001 Jan 1;29(1):308-11
pubmed: 11125122
Front Immunol. 2019 Oct 01;10:2325
pubmed: 31681265
PLoS One. 2017 Feb 2;12(2):e0170843
pubmed: 28152038
Clin Rev Allergy Immunol. 2018 Apr;54(2):261-268
pubmed: 29030829
Nature. 2020 May;581(7809):434-443
pubmed: 32461654
J Allergy Clin Immunol. 2016 Jul;138(1):303-305.e3
pubmed: 26997321
Front Immunol. 2017 Jul 24;8:847
pubmed: 28791010
Biomed Res Int. 2018 May 16;2018:9647253
pubmed: 29888287
Blood. 2016 Jun 23;127(25):3154-64
pubmed: 27114460
Genome Biol. 2019 May 20;20(1):97
pubmed: 31104630
Front Immunol. 2018 May 14;9:636
pubmed: 29867916
J Allergy Clin Immunol. 2017 Jan;139(1):232-245
pubmed: 27577878
Eur J Hum Genet. 2021 Jan;29(1):20-28
pubmed: 32733070
J Allergy Clin Immunol. 2014 Feb;133(2):529-34
pubmed: 24139496
Front Immunol. 2014 Nov 03;5:531
pubmed: 25404929
Nat Genet. 2019 Nov;51(11):1560-1565
pubmed: 31676867
Hum Mutat. 2015 Oct;36(10):922-7
pubmed: 26255989
Sci Rep. 2020 Feb 6;10(1):2057
pubmed: 32029882
J Clin Immunol. 2020 Jul;40(5):729-740
pubmed: 32506361
Front Immunol. 2018 Sep 19;9:2078
pubmed: 30283440
JAMA. 2020 Aug 18;324(7):663-673
pubmed: 32706371
PLoS One. 2014 Dec 11;9(12):e114901
pubmed: 25502423
Nat Rev Genet. 2012 Jul 18;13(8):565-75
pubmed: 22805709
Genet Med. 2019 Jan;21(1):243-251
pubmed: 29921932
J Allergy Clin Immunol. 2018 Apr;141(4):1450-1458
pubmed: 28916186
Nat Rev Genet. 2019 Oct;20(10):582-598
pubmed: 31186537
J Clin Immunol. 2019 Aug;39(6):577-591
pubmed: 31250335
Clin Infect Dis. 2020 Dec 17;71(10):e614-e623
pubmed: 32185379
Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3220-3231
pubmed: 29971439
Genome Res. 2012 Aug;22(8):1525-32
pubmed: 22585873
Nucleic Acids Res. 2019 Jan 8;47(D1):D886-D894
pubmed: 30371827
Scand J Immunol. 2017 Mar;85(3):227-234
pubmed: 28109013
N Engl J Med. 2011 Jul 7;365(1):54-61
pubmed: 21714643
Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):E7128-37
pubmed: 26621750
Hum Mutat. 2015 Oct;36(10):928-30
pubmed: 26220891
Clin Genet. 2020 Sep;98(3):231-239
pubmed: 32441320
Front Immunol. 2016 Nov 07;7:466
pubmed: 27872624
Eur J Med Genet. 2020 May;63(5):103920
pubmed: 32222431
Science. 2007 Aug 3;317(5838):617-9
pubmed: 17673650
J Allergy Clin Immunol. 2015 May;135(5):1380-4.e1-5
pubmed: 25512081
Nucleic Acids Res. 2019 Jan 8;47(D1):D330-D338
pubmed: 30395331
Genet Med. 2019 Apr;21(4):982-986
pubmed: 30279471
J Allergy Clin Immunol. 2016 Jun;137(6):1780-1787
pubmed: 26915675
Nat Genet. 2010 Jan;42(1):30-5
pubmed: 19915526
Immunol Rev. 2020 Sep;297(1):247-272
pubmed: 32640080
Int J Hematol. 2017 Aug;106(2):282-290
pubmed: 28353193
J Allergy Clin Immunol. 2016 Oct;138(4):957-969
pubmed: 27720020
Genome Res. 2010 Jan;20(1):110-21
pubmed: 19858363
Genome Med. 2019 Jun 17;11(1):38
pubmed: 31203817
Genome Biol. 2016 Nov 28;17(1):241
pubmed: 27894357
Nat Rev Genet. 2011 Aug 18;12(9):628-40
pubmed: 21850043
Genet Med. 2017 Feb;19(2):249-255
pubmed: 27854360