Whole-exome Sequencing for the Identification of Rare Variants in Primary Immunodeficiency Genes in Children With Sepsis: A Prospective, Population-based Cohort Study.

Details

Ressource 1Download: 32185379_BIB_D6F373E4D323.pdf (1735.54 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_D6F373E4D323
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Whole-exome Sequencing for the Identification of Rare Variants in Primary Immunodeficiency Genes in Children With Sepsis: A Prospective, Population-based Cohort Study.
Journal
Clinical infectious diseases
Author(s)
Borghesi A., Trück J., Asgari S., Sancho-Shimizu V., Agyeman PKA, Bellos E., Giannoni E., Stocker M., Posfay-Barbe K.M., Heininger U., Bernhard-Stirnemann S., Niederer-Loher A., Kahlert C.R., Natalucci G., Relly C., Riedel T., Kuehni C.E., Thorball C.W., Chaturvedi N., Martinon-Torres F., Kuijpers T.W., Coin L., Wright V., Herberg J., Levin M., Aebi C., Berger C., Fellay J., Schlapbach L.J.
ISSN
1537-6591 (Electronic)
ISSN-L
1058-4838
Publication state
Published
Issued date
17/12/2020
Peer-reviewed
Oui
Volume
71
Number
10
Pages
e614-e623
Language
english
Notes
Publication types: Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes.
We conducted a multicenter, population-based, prospective study including previously healthy children aged ≥28 days and <17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported.
There were 176 children presenting with 185 sepsis episodes who underwent WES (median age, 52 months; interquartile range, 15.4-126.4). There were 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants that were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories, as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants.
Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected variants of uncertain significance in PID genes in 1 out of 5 children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.
Keywords
Adolescent, Child, Cohort Studies, Humans, Middle Aged, Primary Immunodeficiency Diseases, Prospective Studies, Sepsis/genetics, Whole Exome Sequencing, child, exome sequencing, genomics, immunodeficiency, sepsis, variant, variants of uncertain significance
Pubmed
Web of science
Open Access
Yes
Create date
01/04/2020 21:35
Last modification date
05/05/2021 6:36
Usage data