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dc.contributor.authorDasouki, Majed
dc.contributor.authorAlaiya, Ayodeele
dc.contributor.authorElAmin, Tanziel
dc.contributor.authorShinwari, Zakia
dc.contributor.authorMonies, Dorota
dc.contributor.authorAbouelhoda, Mohamed
dc.contributor.authorJabaan, Amjad
dc.contributor.authorAlmourfi, Feras
dc.contributor.authorRahbeeni, Zuhair
dc.contributor.authorAlsohaibani, Fahad
dc.contributor.authorAlmohareb, Fahad
dc.contributor.authorAl-Zahrani, Hazzaa
dc.contributor.authorGuzmán Vega, Francisco J.
dc.contributor.authorArold, Stefan T.
dc.contributor.authorAljurf, Mahmoud
dc.contributor.authorAhmed, Syed Osman
dc.date.accessioned2021-02-28T13:54:38Z
dc.date.available2021-02-28T13:54:38Z
dc.date.issued2021-02
dc.date.submitted2020-06-02
dc.identifier.citationDasouki, M., Alaiya, A., ElAmin, T., Shinwari, Z., Monies, D., Abouelhoda, M., … Ahmed, S. O. (2021). Comprehensive multi-omics analysis of G6PC3 deficiency related congenital neutropenia with inflammatory bowel disease. iScience, 102214. doi:10.1016/j.isci.2021.102214
dc.identifier.issn2589-0042
dc.identifier.doi10.1016/j.isci.2021.102214
dc.identifier.urihttp://hdl.handle.net/10754/667720
dc.description.abstractAutosomal recessive mutations in G6PC3 cause isolated and syndromic congenital neutropenia which includes congenital heart disease and atypical inflammatory bowel disease (IBD). In a highly consanguineous pedigree with novel mutations in G6PC3 and MPL, we performed comprehensive multi-omics analyses. Structural analysis of variant G6PC3 and MPL proteins suggests a damaging effect. A distinct molecular cytokine profile (cytokinome) in the affected proband with IBD was detected. Liquid chromatography-mass spectrometry-based proteomics analysis of the G6PC3 deficient plasma samples identified 460 distinct proteins including 75 upregulated and 73 downregulated proteins. Specifically, the transcription factor GATA4 and LST1 were downregulated while platelet factor 4 (PF4) was upregulated. GATA4 and PF4 have been linked to congenital heart disease and IBD respectively, while LST1 may have perturbed a variety of essential cell functions as it is required for normal cell-cell communication. Together, these studies provide potentially novel insights into the pathogenesis of syndromic congenital G6PC3 deficiency.
dc.description.sponsorshipThe authors wish to thank all the clinicians who provided routine clinical care for these patients and thank the patients and their families who participated in this project. We also acknowledge the Saudi Human Genome Project for infrastructure and informatics support relating to the NGS work. This work was supported by the National Science, Technology, and Innovation Plan program of Saudi Arabia (KACST 13-BIO1978-20). The work by STA and FJGV was supported by the King Abdullah University of Science and Technology (KAUST) through the Award No. FCC/1/1976-25 from the Office of Sponsored Research (OSR).
dc.publisherElsevier BV
dc.relation.urlhttps://linkinghub.elsevier.com/retrieve/pii/S2589004221001826
dc.rightsThis article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleComprehensive multi-omics analysis of G6PC3 deficiency related congenital neutropenia with inflammatory bowel disease
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentStructural Biology and Engineering
dc.identifier.journaliScience
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartment of Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia.
dc.contributor.institutionSaudi Human Genome Program. King Abdulaziz Center for Science & Technology, Riyadh, Saudi Arabia.
dc.contributor.institutionDepartment of Stem Cell Therapy. Proteomics Program. King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia.
dc.contributor.institutionDepartment of Medical Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia.
dc.contributor.institutionDepartment of Internal Medicine, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia.
dc.contributor.institutionAdult hematology/BMT, King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia.
dc.contributor.institutionCentre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, 34090 Montpellier, France.
dc.identifier.pages102214
kaust.personGuzmán Vega, Francisco J.
kaust.personArold, Stefan T.
kaust.grant.numberFCC/1/1976-25
dc.date.accepted2021-02-17
refterms.dateFOA2021-02-28T13:56:09Z
kaust.acknowledged.supportUnitOffice of Sponsored Research (OSR)


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This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.
Except where otherwise noted, this item's license is described as This article is available under the Creative Commons CC-BY-NC-ND license and permits non-commercial use of the work as published, without adaptation or alteration provided the work is fully attributed.