Characterization of AR-CGD female patient with a novel homozygous deletion in CYBC1 gene presenting with unusual clinical phenotype

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2023-06, Vol.251, p.109316-109316, Article 109316
• Main Authors: Chiriaco, Maria, De Matteis, Arianna, Cifaldi, Cristina, Di Matteo, Gigliola, Rivalta, Beatrice, Passarelli, Chiara, Perrone, Chiara, Novelli, Antonio, De Benedetti, Fabrizio, Insalaco, Antonella, Palma, Paolo, Finocchi, Andrea
• Format: Article
• Language: English
• Subjects: AR-CGD5; CYBC1/EROS NADPH oxidase activity; Female; Granulomatous Disease, Chronic - diagnosis; Granulomatous Disease, Chronic - genetics; Homozygote; Humans; Inflammation; Mutation; NADPH Oxidases - genetics; Phenotype; Sequence Deletion - genetics
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2023.109316

Chronic granulomatous disease (CGD) is a human IEI caused by mutations in genes encoding the NADPH oxidase subunits, the enzyme responsible for the respiratory burst. CGD patients have severe life-threatening infections, hyperinflammation and immune dysregulation. Recently, an additional autosomal recessive AR-CGD (type 5) caused by mutations in CYBC1/EROS gene was identified. We report a AR-CGD5 patient with a novel loss of function (LOF) homozygous deletion c.8_7del in the CYBC1 gene including the initiation ATG codon that leads to failure of CYBC1/EROS protein expression and presenting with an unusual clinical manifestation of childhood-onset sarcoidosis-like disease requiring multiple immunosuppressive therapies. We described an abnormal gp91phox protein expression/function in the patient's neutrophils and monocytes (about 50%) and a severely compromised B cell subset (gp91phox