Is gene panel sequencing more efficient than clinical-based gene sequencing to diagnose autoinflammatory diseases? A randomized study.
Sanger sequencing
genetic testing
hereditary autoinflammatory diseases
targeted next-generation sequencing
Journal
Clinical and experimental immunology
ISSN: 1365-2249
Titre abrégé: Clin Exp Immunol
Pays: England
ID NLM: 0057202
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
17
04
2020
revised:
31
07
2020
accepted:
12
08
2020
pubmed:
11
9
2020
medline:
27
7
2021
entrez:
10
9
2020
Statut:
ppublish
Résumé
The aim of this study was to compare the effectiveness of the gene-panel next-generation sequencing (NGS) strategy versus the clinical-based gene Sanger sequencing for the genetic diagnosis of autoinflammatory diseases (AIDs). Secondary goals were to describe the gene and mutation distribution in AID patients and to evaluate the impact of the genetic report on the patient's medical care and treatment. Patients with AID symptoms were enrolled prospectively and randomized to two arms, NGS (n = 99) (32-55 genes) and Sanger sequencing (n = 197) (one to four genes). Genotypes were classified as 'consistent/confirmatory', 'uncertain significance' or 'non-contributory'. The proportion of patients with pathogenic genotypes concordant with the AID phenotype (consistent/confirmatory) was significantly higher with NGS than Sanger sequencing [10 of 99 (10·1%) versus eight of 197 (4·1%)]. MEFV, ADA2 and MVK were the most represented genes with a consistent/confirmed genotype, whereas MEFV, NLRP3, NOD2 and TNFRSF1A were found in the 'uncertain significance' genotypes. Six months after the genetic report was sent, 54 of 128 (42·2%) patients had received effective treatment for their symptoms; 13 of 128 (10·2%) had started treatment after the genetic study. For 59 of 128 (46%) patients, the results had an impact on their overall care, independent of sequencing group and diagnostic conclusion. Targeted NGS improved the diagnosis and global care of patients with AIDs.
Identifiants
pubmed: 32909274
doi: 10.1111/cei.13511
pmc: PMC7744495
doi:
Banques de données
ClinicalTrials.gov
['NCT02976948']
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105-114Informations de copyright
© 2020 British Society for Immunology.
Références
J Med Genet. 2018 Aug;55(8):530-537
pubmed: 29599418
PLoS One. 2017 Jul 27;12(7):e0181874
pubmed: 28750028
Nat Genet. 1997 Sep;17(1):25-31
pubmed: 9288094
Hum Mutat. 2016 Jun;37(6):564-9
pubmed: 26931183
Semin Arthritis Rheum. 2016 Apr;45(5):633-7
pubmed: 26620106
Rheumatol Int. 2019 May;39(5):911-919
pubmed: 30783801
Ann Rheum Dis. 2015 May;74(5):799-805
pubmed: 25637003
Genet Med. 2015 May;17(5):405-24
pubmed: 25741868
Eur J Hum Genet. 2018 Jul;26(7):960-971
pubmed: 29681619
Oral Dis. 2016 Oct;22(7):591-604
pubmed: 26837051
J Clin Med. 2019 Oct 18;8(10):
pubmed: 31635385
Rheumatology (Oxford). 2014 Nov;53(11):1927-39
pubmed: 24831056
Semin Immunopathol. 2015 Jul;37(4):359-62
pubmed: 25998913
Eur J Hum Genet. 2001 Jul;9(7):473-83
pubmed: 11464238