A novel mutation in EROS (CYBC1) causes Chronic Granulomatous Disease

• DOI: 10.1101/2023.04.21.23286144
• Publication Date: 2023-04-25T18:02:55Z
• Authors: Paige M Mortimer; Esme Nichols; Joe Thomas; Rachna Shanbhag; Neha Singh; Eve L Coomber; Talat H Malik; Matthew C Pickering; Lyra Randzavola; William Rae; Sagar Bhattad; David C Thomas
• Keywords: Phagocytes; Mutation; Humans; NADPH Oxidases; Granulomatous Disease, Chronic; Reactive Oxygen Species; 3. Good health

AbstractChronic Granulomatous Disease (CGD) is an inborn error of immunity characterised by opportunistic infection and sterile granulomatous inflammation. CGD is caused by a failure of reactive oxygen species (ROS) production by the phagocyte NADPH oxidase. Mutations in the genes encoding phagocyte NADPH oxidase subunits cause CGD. We and others have described a novel form of CGD (CGD5) secondary to lack of EROS (CYBC1), a highly selective chaperone for gp91phox. EROS-deficient cells express minimal levels of gp91phoxand its binding partner p22phox, but EROS also controls the expression of other proteins such as P2×7. The full nature of CGD5 is currently unknown. We describe a homozygous frameshift mutation inCYBC1leading to CGD. Individuals who are heterozygous for this mutation are found in South Asian populations (allele frequency = 0.00006545), thus it is not a private mutation. Therefore, it is likely to be the underlying cause of other cases of CGD.