دورية أكاديمية
Comprehensive multi-omics analysis of G6PC3 deficiency related congenital neutropenia with inflammatory bowel disease
| العنوان: | Comprehensive multi-omics analysis of G6PC3 deficiency related congenital neutropenia with inflammatory bowel disease |
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| المؤلفون: | Dasouki, Majed, Alaiya, Ayodeele, ElAmin, Tanziel, Shinwari, Zakia, Monies, Dorota, Abouelhoda, Mohamed, Jabaan, Amjad, Almourfi, Feras, Rahbeeni, Zuhair, Alsohaibani, Fahad, Almohareb, Fahad, Al-Zahrani, Hazzaa, Guzmán Vega, Francisco J., Arold, Stefan T., Aljurf, Mahmoud, Ahmed, Syed Osman |
| المساهمون: | Biological and Environmental Science and Engineering (BESE) Division, Bioscience Program, Computational Bioscience Research Center (CBRC), Structural Biology and Engineering, Department of Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia., Saudi Human Genome Program. King Abdulaziz Center for Science & Technology, Riyadh, Saudi Arabia., Department of Stem Cell Therapy. Proteomics Program. King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia., Department of Medical Genetics, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia., Department of Internal Medicine, King Faisal Specialist Hospital, and Research Center, Riyadh Saudi Arabia., Adult hematology/BMT, King Faisal Specialist Hospital and Research Center, Riyadh Saudi Arabia., Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, 34090 Montpellier, France. |
| بيانات النشر: | Elsevier BV |
| سنة النشر: | 2021 |
| المجموعة: | King Abdullah University of Science and Technology: KAUST Repository |
| الوصف: | Autosomal 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. ; The 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). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 2589-0042 |
| العلاقة: | https://linkinghub.elsevier.com/retrieve/pii/S2589004221001826Test; Dasouki, 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; iScience; 102214; http://hdl.handle.net/10754/667720Test |
| DOI: | 10.1016/j.isci.2021.102214 |
| الإتاحة: | https://doi.org/10.1016/j.isci.2021.102214Test http://hdl.handle.net/10754/667720Test |
| حقوق: | 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. ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ |
| رقم الانضمام: | edsbas.7BFA809D |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 25890042 |
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| DOI: | 10.1016/j.isci.2021.102214 |