Novel RAG1 mutation and the occurrence of mycobacterial and Chromobacterium violaceum infections in a case of leaky SCID.
Microb Pathog
; 109: 114-119, 2017 Aug.
Article
en En
| MEDLINE
| ID: mdl-28552805
ABSTRACT
Severe combined immunodeficiency (SCID) is a potentially fatal primary immunodeficiency (PID) that is caused by mutations in genes such as IL2RG, JAK3, IL7RA, RAG1, RAG2, and ADA. The products of these genes are involved in the development of several immune cells such as T, B and natural killer (NK) cells. Most of the SCID forms are autosomal recessive with the exception of IL2RG defects that cause an X-linked SCID. Among the different SCID types, there is a rare SCID form called leaky SCID, which is less severe when compared to the other classical SCID phenotypes. Leaky SCID can be caused by hypomorphic mutations in RAG1 and RAG2 that result in only partial loss of enzymatic function of the proteins respectively encoded by these genes. Here we report a novel missense mutation (c. 307C > T/p.H103Y) in the RAG1 gene in a patient with leaky SCID. In addition, we characterize the clinical and immunological features of this patient that developed along with other severe and recurrent infections such as mycobacterial diseases (BCGitis and pulmonary tuberculosis), the first occurrence of Chromobacterium violaceum in a patient with SCID. Understanding the increased susceptibility to mycobacteria presented by the patient, in which a functional investigation of IL-12/IFN-γ axis was performed, which demonstrated reduced production of IFN-γ in the supernatans of peripheral blood mononuclear cell cultures from the patient compared with those from healthy subjects. In conclusion, our data expands the molecular and clinical spectrum associated with the leaky SCID phenotype.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Chromobacterium
/
Inmunodeficiencia Combinada Grave
/
Proteínas de Homeodominio
/
Mutación Missense
/
Mycobacterium
Límite:
Female
/
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Microb Pathog
Asunto de la revista:
DOENCAS TRANSMISSIVEIS
/
MICROBIOLOGIA
Año:
2017
Tipo del documento:
Article