title: Genetic disorders coupled to ROS deficiency.
abstract: Maintaining the redox balance between generation and elimination of reactive oxygen species (ROS) is critical for health. Disturbances such as continuously elevated ROS levels will result in oxidative stress and development of disease, but likewise, insufficient ROS production will be detrimental to health. Reduced or even complete loss of ROS generation originates mainly from inactivating variants in genes encoding for NADPH oxidase complexes. In particular, deficiency in phagocyte Nox2 oxidase function due to genetic variants (CYBB, CYBA, NCF1, NCF2, NCF4) has been recognized as a direct cause of chronic granulomatous disease (CGD), an inherited immune disorder. More recently, additional diseases have been linked to functionally altered variants in genes encoding for other NADPH oxidases, such as for DUOX2/DUOXA2 in congenital hypothyroidism, or for the Nox2 complex, NOX1 and DUOX2 as risk factors for inflammatory bowel disease. A comprehensive overview of novel developments in terms of Nox/Duox-deficiency disorders is presented, combined with insights gained from structure-function studies that will aid in predicting functional defects of clinical variants.
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Sharon
authors.initials: S
authors.lastname: O'Neill
authors.affiliation: Université Grenoble Alpes, TIMC-IMAG Pôle Biologie, CHU de Grenoble, Grenoble, France; CGD Diagnosis and Research Centre, Pôle Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Brault
authors.affiliation: Université Grenoble Alpes, TIMC-IMAG Pôle Biologie, CHU de Grenoble, Grenoble, France; CGD Diagnosis and Research Centre, Pôle Biologie, CHU de Grenoble, Grenoble, France.
authors.forename: Marie-Jose
authors.initials: MJ
authors.lastname: Stasia
authors.affiliation: Conway Institute, University College Dublin, Dublin, Ireland. Electronic address: ulla.knaus@ucd.ie.
authors.forename: Ulla G
authors.initials: UG
authors.lastname: Knaus
mesh_terms: D002318:Cardiovascular Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D003920:Diabetes Mellitus / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D000074623:Dual Oxidases; D015870:Gene Expression; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007037:Hypothyroidism / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D009154:Mutation; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C513411:DUOXA2 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D000074623:Dual Oxidases; C056558:CYBB protein, human; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C431515:DUOX2 protein, human
keywords: Chronic granulomatous disease; DUOX; Genetic disease; Hypothyroidism; Inflammatory bowel disease; NADPH oxidase; NOX; Reactive oxygen species (ROS)