Please use this identifier to cite or link to this item: http://docs.prosentient.com.au/prosentientjspui/handle/1/11132
Title: Exome Sequencing Reveals Primary Immunodeficiencies in Children with Community-Acquired Pseudomonas aeruginosa Sepsis.
Authors: Asgari, Samira
McLaren, Paul J
Peake, Jane
Wong, Melanie
Wong, Richard
Bartha, Istvan
Francis, Joshua R
Abarca, Katia
Gelderman, Kyra A
Agyeman, Philipp
Aebi, Christoph
Berger, Christoph
Fellay, Jacques
Schlapbach, Luregn J
Affiliation: Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland..
National HIV and Retrovirology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada..
Lady Cilento Children's Hospital , Brisbane, QLD , Australia..
Children's Hospital Westmead , Sydney, NSW , Australia..
Pathology Queensland Central Laboratory, Royal Brisbane and Women's Hospital , Brisbane, QLD , Australia..
Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland..
Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia; Royal Darwin Hospital, Darwin, NT, Australia..
Departamento de Enfermedades Infecciosas e Inmunología Pediátrica, Escuela de Medicina, Pontificia Universidad Católica de Chile , Santiago , Chile..
Sanquin Diagnostic Services , Amsterdam , Netherlands..
Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , Bern , Switzerland..
Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern , Bern , Switzerland..
University Children's Hospital Zurich , Zurich , Switzerland..
Global Health Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland..
Lady Cilento Children's Hospital, Brisbane, QLD, Australia; Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; Paediatric Critical Care Research Group (PCCRG), Mater Research, University of Queensland, Brisbane, QLD, Australia..
Issue Date: 2016
Citation: Frontiers in immunology 2016; 7: 357
Abstract: One out of three pediatric sepsis deaths in high income countries occur in previously healthy children. Primary immunodeficiencies (PIDs) have been postulated to underlie fulminant sepsis, but this concept remains to be confirmed in clinical practice. Pseudomonas aeruginosa (P. aeruginosa) is a common bacterium mostly associated with health care-related infections in immunocompromised individuals. However, in rare cases, it can cause sepsis in previously healthy children. We used exome sequencing and bioinformatic analysis to systematically search for genetic factors underpinning severe P. aeruginosa infection in the pediatric population. We collected blood samples from 11 previously healthy children, with no family history of immunodeficiency, who presented with severe sepsis due to community-acquired P. aeruginosa bacteremia. Genomic DNA was extracted from blood or tissue samples obtained intravitam or postmortem. We obtained high-coverage exome sequencing data and searched for rare loss-of-function variants. After rigorous filtrations, 12 potentially causal variants were identified. Two out of eight (25%) fatal cases were found to carry novel pathogenic variants in PID genes, including BTK and DNMT3B. This study demonstrates that exome sequencing allows to identify rare, deleterious human genetic variants responsible for fulminant sepsis in apparently healthy children. Diagnosing PIDs in such patients is of high relevance to survivors and affected families. We propose that unusually severe and fatal sepsis cases in previously healthy children should be considered for exome/genome sequencing to search for underlying PIDs.
URI: http://docs.prosentient.com.au/prosentientjspui/handle/1/11132
DOI: 10.3389/fimmu.2016.00357
ISSN: 1664-3224
Type: Journal Article
Subjects: Pseudomonas
bacteremia
child
exome sequencing
primary immunodeficiency
sepsis
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