Please use this identifier to cite or link to this item: https://dora.health.qld.gov.au/qldresearchjspui/handle/1/5063
Title: Whole-exome sequencing for the identification of rare variants in primary immunodeficiency genes in children with sepsis: A prospective, population-based cohort study
Authors: Kuijpers, T. W.
Niederer-Loher, A.
Kahlert, C. R.
Natalucci, G.
Relly, C.
Riedel, T.
Kuehni, C. E.
Thorball, C. W.
Chaturvedi, N.
Martinon-Torres, F.
Bernhard-Stirnemann, S.
Coin, L.
Wright, V.
Herberg, J.
Levin, M.
Aebi, C.
Berger, C.
Fellay, J.
Schlapbach, L. J.
Borghesi, A.
Trück, J.
Asgari, S.
Sancho-Shimizu, V.
Agyeman, P. K. A.
Bellos, E.
Giannoni, E.
Stocker, M.
Posfay-Barbe, K. M.
Heininger, U.
Issue Date: 2020
Source: 71, (10), 2020, p. E614-E623
Pages: E614-E623
Journal: Clinical Infectious Diseases
Abstract: Background. 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. Methods. 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. Results. 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. Conclusions. 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.L20107154442021-02-08
2021-03-17
DOI: 10.1093/cid/ciaa290
Resources: https://www.embase.com/search/results?subaction=viewrecord&id=L2010715444&from=exporthttp://dx.doi.org/10.1093/cid/ciaa290 |
Keywords: infant;irak1 gene;irf2bp2 gene;kdm6a gene;kmt2d gene;major clinical study;male;multicenter study;Neisseria meningitidis;newborn;nfat5 gene;nfkb2 gene;samd9 gene;sema3e gene;Staphylococcus aureus;stat3 gene;Streptococcus agalactiae;Streptococcus group A;Streptococcus pneumoniae;tcf3 gene;tnfrsf13b gene;was gene;whole exome sequencing;HiSeq 2500;tbx1 gene;nonhuman;observational study;pad gene;pd gene;pediatric hospital;plcg2 gene;pola1 gene;population research;priority journal;prospective study;pten gene;rare disease;KEK-029/11genetic analyzer;adolescent;aid gene;article;bach2 gene;bacteremia;bcl11b gene;blood culture;c4a gene;cfh gene;chd7 gene;child;clinical feature;cohort analysis;community acquired infection;controlled study;cxcr4 gene;cybb gene;female;gene;genetic susceptibility;genetic variability;genetic variation;Haemophilus influenzae;homozygote;hospital admission;human;il17f gene;immune deficiency
Type: Article
Appears in Sites:Children's Health Queensland Publications

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