Immune dysregulation associated with co-occurring germline CBL and SH2B3 variants.
Hum Genomics
; 16(1): 40, 2022 09 19.
Article
em En
| MEDLINE
| ID: mdl-36123612
ABSTRACT
BACKGROUND:
CBL syndrome is a RASopathy caused by heterozygous germline mutations of the Casitas B-lineage lymphoma (CBL) gene. It is characterized by heterogeneous clinical phenotype, including developmental delay, facial dysmorphisms, cardiovascular malformations and an increased risk of cancer development, particularly juvenile myelomonocytic leukemia (JMML). Although the clinical phenotype has been progressively defined in recent years, immunological manifestations have not been well elucidated to date.METHODS:
We studied the genetic, immunological, coagulative, and clinical profile of a family with CBL syndrome that came to our observation after the diagnosis of JMML, with homozygous CBL mutation, in one of the members.RESULTS:
Variant analysis revealed the co-occurrence of CBL heterozygous mutation (c.1141 T > C) and SH2B3 mutation (c.1697G > A) in two other members. Patients carrying both mutations showed an ALPS-like phenotype characterized by lymphoproliferation, cytopenia, increased double-negative T-cells, impaired Fas-mediated lymphocyte apoptosis, altered cell death in PBMC and low TRECs expression. A coagulative work-up was also performed and showed the presence of subclinical coagulative alterations in patients carrying both mutations.CONCLUSION:
In the reported family, we described immune dysregulation, as part of the clinical spectrum of CBL mutation with the co-occurrence of SH2B3.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas c-cbl
/
Leucemia Mielomonocítica Juvenil
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Itália