Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency
Scott Drutman, Davood Mansouri, Seyed Alireza Mahdaviani, Anna‐Lena Neehus, David Hum, Ruslana Bryk, Nicholas Hernandez, Serkan Belkaya, Franck Rapaport, Benedetta Bigio, Robert O. Fisch, Mahbuba Rahman, Taushif Khan, Fatima Al Ali, Majid Marjani, Nahal Mansouri, Lazaro Lorenzo, Jean‐François Emile, Nico Marr, Emmanuelle Jouanguy, Jacinta Bustamante, Laurent Abel, Stéphanie Boisson‐Dupuis, Vivien Béziat, Carl Nathan, Jean‐Laurent Casanova
Abstract
BACKGROUND: ) are susceptible to the related murine CMV infection. METHODS: We studied a previously healthy 51-year-old man from Iran who after acute CMV infection had an onset of progressive CMV disease that led to his death 29 months later. We hypothesized that the patient may have had a novel type of inborn error of immunity. Thus, we performed whole-exome sequencing and tested candidate mutant alleles experimentally. RESULTS: variants that we found in homozygosity in public databases encoded functional proteins, as did all other variants with an allele frequency greater than 0.001. CONCLUSIONS: These findings suggest that inherited NOS2 deficiency was clinically silent in this patient until lethal infection with CMV. Moreover, NOS2 appeared to be redundant for control of other pathogens in this patient. (Funded by the National Center for Advancing Translational Sciences and others.).