Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency.

Détails

ID Serval
serval:BIB_03EBED9B2895
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fatal Cytomegalovirus Infection in an Adult with Inherited NOS2 Deficiency.
Périodique
The New England journal of medicine
Auteur(s)
Drutman S.B., Mansouri D., Mahdaviani S.A., Neehus A.L., Hum D., Bryk R., Hernandez N., Belkaya S., Rapaport F., Bigio B., Fisch R., Rahman M., Khan T., Al Ali F., Marjani M., Mansouri N., Lorenzo-Diaz L., Emile J.F., Marr N., Jouanguy E., Bustamante J., Abel L., Boisson-Dupuis S., Béziat V., Nathan C., Casanova J.L.
ISSN
1533-4406 (Electronic)
ISSN-L
0028-4793
Statut éditorial
Publié
Date de publication
30/01/2020
Peer-reviewed
Oui
Volume
382
Numéro
5
Pages
437-445
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Résumé
Cytomegalovirus (CMV) can cause severe disease in children and adults with a variety of inherited or acquired T-cell immunodeficiencies, who are prone to multiple infections. It can also rarely cause disease in otherwise healthy persons. The pathogenesis of idiopathic CMV disease is unknown. Inbred mice that lack the gene encoding nitric oxide synthase 2 (Nos2) are susceptible to the related murine CMV infection.
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.
We found a homozygous frameshift mutation in NOS2 encoding a truncated NOS2 protein that did not produce nitric oxide, which determined that the patient had autosomal recessive NOS2 deficiency. Moreover, all NOS2 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.
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.).
Pubmed
Création de la notice
31/01/2020 16:55
Dernière modification de la notice
07/07/2021 5:37
Données d'usage