Lipinski, Simone, Petersen, Britt-Sabina, Barann, Matthias, Piecyk, Agnes ORCID: 0000-0002-9582-121X, Tran, Florian, Mayr, Gabriele, Jentzsch, Marlene, Aden, Konrad ORCID: 0000-0003-3482-7316, Stengel, Stephanie T., Klostermeier, Ulrich C., Sheth, Vrunda, Ellinghaus, David, Rausch, Tobias ORCID: 0000-0001-5773-5620, Korbel, Jan O., Nothnagel, Michael ORCID: 0000-0001-8305-7114, Krawczak, Michael ORCID: 0000-0003-2603-1502, Gilissen, Christian ORCID: 0000-0003-1693-9699, Veltman, Joris A., Forster, Michael ORCID: 0000-0001-9927-5124, Forster, Peter, Lee, Clarence C., Fritscher-Ravens, Annette, Schreiber, Stefan, Franke, Andre and Rosenstiel, Philip ORCID: 0000-0002-9692-8828 (2019). Missense variants in NOX1 and p22phox in a case of very-early-onset inflammatory bowel disease are functionally linked to NOD2. Cold Spring Harb. Mol. Case Stud., 5 (1). COLD SPRING HARBOR: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT. ISSN 2373-2873

Full text not available from this repository.

Abstract

Whole-genome and whole-exome sequencing of individual patients allow the study of rare and potentially causative genetic variation. In this study, we sequenced DNA of a trio comprising a boy with very-early-onset inflammatory bowel disease (veoIBD) and his unaffected parents. We identified a rare, X-linked missense variant in the NAPDH oxidase NOX1 gene (c.C721T, p.R241C) in heterozygous state in the mother and in hemizygous state in the patient. We discovered that, in addition, the patient was homozygous for a common missense variant in the CYBA gene (c.T214C, p.Y72H). CYBA encodes the p22phox protein, a cofactor for NOX1. Functional assays revealed reduced cellular ROS generation and antibacterial capacity of NOX1 and p22phox variants in intestinal epithelial cells. Moreover, the identified NADPH oxidase complex variants affected NOD2-mediated immune responses, and p22phox was identified as a novel NOD2 interactor. In conclusion, we detected missense variants in a veoIBD patient that disrupt the host response to bacterial challenges and reduce protective innate immune signaling via NOD2. We assume that the patient's individual genetic makeup favored disturbed intestinal mucosal barrier function.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lipinski, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petersen, Britt-SabinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barann, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piecyk, AgnesUNSPECIFIEDorcid.org/0000-0002-9582-121XUNSPECIFIED
Tran, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayr, GabrieleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jentzsch, MarleneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aden, KonradUNSPECIFIEDorcid.org/0000-0003-3482-7316UNSPECIFIED
Stengel, Stephanie T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klostermeier, Ulrich C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sheth, VrundaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ellinghaus, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rausch, TobiasUNSPECIFIEDorcid.org/0000-0001-5773-5620UNSPECIFIED
Korbel, Jan O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothnagel, MichaelUNSPECIFIEDorcid.org/0000-0001-8305-7114UNSPECIFIED
Krawczak, MichaelUNSPECIFIEDorcid.org/0000-0003-2603-1502UNSPECIFIED
Gilissen, ChristianUNSPECIFIEDorcid.org/0000-0003-1693-9699UNSPECIFIED
Veltman, Joris A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Forster, MichaelUNSPECIFIEDorcid.org/0000-0001-9927-5124UNSPECIFIED
Forster, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Clarence C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fritscher-Ravens, AnnetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rosenstiel, PhilipUNSPECIFIEDorcid.org/0000-0002-9692-8828UNSPECIFIED
URN: urn:nbn:de:hbz:38-158050
DOI: 10.1101/mcs.a002428
Journal or Publication Title: Cold Spring Harb. Mol. Case Stud.
Volume: 5
Number: 1
Date: 2019
Publisher: COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
Place of Publication: COLD SPRING HARBOR
ISSN: 2373-2873
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NADPH OXIDASE; CROHNS-DISEASE; GENETIC-VARIATION; RECEPTOR 1; EXPRESSION; MUTATIONS; SUSCEPTIBILITY; GENERATION; PROTEIN; GUTMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/15805

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item