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@article{Borghesi:2020:cid/ciaa290,
author = {Borghesi, A and Trück, J and Asgari, S and Sancho-Shimizu, V and Agyeman, PKA and Bellos, E and Giannoni, E and Stocker, M and Posfay-Barbe, KM and Heininger, U and Bernhard-Stirnemann, S and Niederer-Loher, A and Kahlert, CR and Natalucci, G and Relly, C and Riedel, T and Kuehni, CE and Thorball, CW and Chaturvedi, N and Martinon-Torres, F and Kuijpers, TW and Coin, L and Wright, V and Herberg, J and Levin, M and Aebi, C and Berger, C and Fellay, J and Schlapbach, LJ and EUCLIDS, consortium and the Swiss Paediatric Sepsis Study},
doi = {cid/ciaa290},
journal = {Clinical Infectious Diseases},
pages = {e614--e623},
title = {Whole-exome sequencing for the identification of rare variants in primary immunodeficiency genes in children with sepsis - a prospective population-based cohort study.},
url = {http://dx.doi.org/10.1093/cid/ciaa290},
volume = {71},
year = {2020}
}

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TY  - JOUR
AB  - 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: Multicenter population-based prospective study including previously healthy children ≥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: 176 children presenting with 185 sepsis episodes underwent WES (median age 52 months, IQR 15.4-126.4). 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) were found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants which 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 one out of five children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.
AU  - Borghesi,A
AU  - Trück,J
AU  - Asgari,S
AU  - Sancho-Shimizu,V
AU  - Agyeman,PKA
AU  - Bellos,E
AU  - Giannoni,E
AU  - Stocker,M
AU  - Posfay-Barbe,KM
AU  - Heininger,U
AU  - Bernhard-Stirnemann,S
AU  - Niederer-Loher,A
AU  - Kahlert,CR
AU  - Natalucci,G
AU  - Relly,C
AU  - Riedel,T
AU  - Kuehni,CE
AU  - Thorball,CW
AU  - Chaturvedi,N
AU  - Martinon-Torres,F
AU  - Kuijpers,TW
AU  - Coin,L
AU  - Wright,V
AU  - Herberg,J
AU  - Levin,M
AU  - Aebi,C
AU  - Berger,C
AU  - Fellay,J
AU  - Schlapbach,LJ
AU  - EUCLIDS,consortium and the Swiss Paediatric Sepsis Study
DO  - cid/ciaa290
EP  - 623
PY  - 2020///
SN  - 1058-4838
SP  - 614
TI  - Whole-exome sequencing for the identification of rare variants in primary immunodeficiency genes in children with sepsis - a prospective population-based cohort study.
T2  - Clinical Infectious Diseases
UR  - http://dx.doi.org/10.1093/cid/ciaa290
UR  - https://www.ncbi.nlm.nih.gov/pubmed/32185379
UR  - https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa290/5809292
UR  - http://hdl.handle.net/10044/1/77634
VL  - 71
ER  -

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